Bayer Plc v NHS Darlington CCG and Others
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| Back of an eye showing age-related macular degeneration
Author US National Eye Institute
Source Wikipedia |
Jane Lambert
Administrative Court (Mrs Justice Whipple) Bayer Plc v NHS Darlington CCG and others [2018] EWHC 2465 (Admin) 21 Sept 2018
This case was an application by Bayer Plc and Novartis Pharmaceuticals UK Ltd. for judicial review of a decision by 12 clinical commissioning groups ("CCGs") in Northeast England to offer patients with wet AMD (age-related macular degeneration) injections of a drug known as Avastin or bevacizumab. The reason for their decision is that Avastin costs £28 per injection compared to £816 for Bayer's EYLEA and £551 for Novartis's Lucentis. The CCGs had made their decision to save money. The only problem was that Avastin had been developed for the treatment of cancer and not ophthalmology whereas the other two drugs had been authorized by the European Medicines Agency for treating wet AMD.
The Challenge
Avastin inhibits a protein known as vascular endothelial growth factor ("VGEF") that stimulates the growth of blood vessels behind the macula of the retina and causes wet AMD. Roche, which manufactured the drug, had obtained marketing authorization for Avantis to treat colorectal and other cancers but had never sought marketing authorization for opthalmic use.
Bayer and Novartis argued that the CCGs could not authorize the prescription of medicines that had not received marketing authorization from the EMA. Mrs Justice Whipple set out the grounds on which Bayer and Novartis challenged the decision at paragraph [5] of her judgment:
"i) it is premised on an error of law, namely that there is a lawful basis for the supply of Avastin to treat wet AMD patients;
ii) it fundamentally undermines the objective of Directive 2001/83/EC on the Community code relating to medicinal products for human use (the "Directive") and constitutes a breach of the duty of sincere cooperation in Article 4(3) of the Treaty of the European Union ("TEU");
iii) it undermines patients' rights of access to NICE recommended treatments;
iv) it introduces information for the patients (by means of a Q&A document and a Patient Information Leaflet which accompany the policy) which are misleading and inaccurate in material respects."
The Issues
Her ladyship summarized the issues before her as follows at paragraph [139]:
"i) Does the EMA have exclusive competence to determine whether Avastin is effective and/or clinically effective for ophthalmic use?
ii) Can treating clinicians lawfully choose Avastin on grounds of cost?
iii) Is Avastin safe for ophthalmic use?
iv) Is there a mature and established market in compounded bevacizumab prepared for ophthalmic use?
v) Is compounded bevacizumab an unlicensed medicine or an off-label use of a licensed medicine?
vi) What is the relevant test by which the lawfulness of the Policy is to be judged, in domestic law?"
"Does the EMA have exclusive competence to determine whether Avastin is effective and/or clinically effective for ophthalmic use?"
Bayer and Novartis argued that the EMA has exclusive competence to determine the safety, clinical efficacy and quality of medicines available to the public. They based their argument on their construction of Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use.
The judge rejected the claimants' argument. In her view, the National Institute for Health and Care Excellence ("NICE") and the CCGs were competent to assess whether Avastin is an effective drug in treating wet AMD, to assess its overall clinical effectiveness for that purpose taking account of safety and cost, and to conduct that assessment by comparing it to the other medicines available to treat wet AMD. She set out her reasons at paragraph [144]:
"i) The EMA is established by the Directive and its role is limited by the Directive. The EMA (and its domestic counterpart, the MHRA) have exclusive competence to determine whether to recommend that a medicine should be granted a marketing authorisation for any particular therapeutic purpose for which the manufacturer seeks such an authorisation. That function is integral to the harmonised system in the Directive. When presented with an application for a marketing authorisation, the EMA assesses the efficacy and safety of the medicine for the proposed use, based on the information provided to the EMA by the applicant. The EMA conducts no wider enquiry into the efficacy of that medicine for treating other conditions, or the relative efficacy of that medicine when compared with other medicines which are available for the same use.
ii) Roche, the manufacturer of Avastin, has not asked for a marketing authorisation to extend to ophthalmic use. The decision not to seek a marketing authorisation for ophthalmic use is Roche's to make. But the fact that Roche has not chosen to seek a marketing authorisation for ophthalmic use demonstrates the limits of the EMA's role. The EMA is simply not involved in the wider consideration of Avastin for ophthalmic use; nor could it be, unless and until Roche asks it to be.
iii) The consequence of that is not, as the Claimants seek to argue, that the national healthcare authorities are prohibited from considering the efficacy or safety of Avastin to treat wet AMD. 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.
iv) The role of the national authorities in assessing clinical effectiveness is recognised in the domestic statutory framework establishing NICE and the CCGs. It is recognised in the domestic case law (the line of authority from ex p A onwards, see above), and it is recognised in the case law of the CJEU (the Duphar line of authority, ABPI in particular). It is fundamental to the operation of a rational and effective public health system.
v) In carrying out that role, the national authorities are entitled to look at all and any evidence available to them in relation to the efficacy, cost and risk associated with the use of that medicine for the therapeutic purpose envisaged. The review is not limited, as the EMA's would be, to the material provided by the manufacturer; nor is the review limited to determining questions of efficacy and safety of that medicine, alone. The national authorities are at liberty to assess the comparative clinical effectiveness (including value for money) of any medicine."
"i) The EMA is established by the Directive and its role is limited by the Directive. The EMA (and its domestic counterpart, the MHRA) have exclusive competence to determine whether to recommend that a medicine should be granted a marketing authorisation for any particular therapeutic purpose for which the manufacturer seeks such an authorisation. That function is integral to the harmonised system in the Directive. When presented with an application for a marketing authorisation, the EMA assesses the efficacy and safety of the medicine for the proposed use, based on the information provided to the EMA by the applicant. The EMA conducts no wider enquiry into the efficacy of that medicine for treating other conditions, or the relative efficacy of that medicine when compared with other medicines which are available for the same use.
ii) Roche, the manufacturer of Avastin, has not asked for a marketing authorisation to extend to ophthalmic use. The decision not to seek a marketing authorisation for ophthalmic use is Roche's to make. But the fact that Roche has not chosen to seek a marketing authorisation for ophthalmic use demonstrates the limits of the EMA's role. The EMA is simply not involved in the wider consideration of Avastin for ophthalmic use; nor could it be, unless and until Roche asks it to be.
iii) The consequence of that is not, as the Claimants seek to argue, that the national healthcare authorities are prohibited from considering the efficacy or safety of Avastin to treat wet AMD. 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.
iv) The role of the national authorities in assessing clinical effectiveness is recognised in the domestic statutory framework establishing NICE and the CCGs. It is recognised in the domestic case law (the line of authority from ex p A onwards, see above), and it is recognised in the case law of the CJEU (the Duphar line of authority, ABPI in particular). It is fundamental to the operation of a rational and effective public health system.
v) In carrying out that role, the national authorities are entitled to look at all and any evidence available to them in relation to the efficacy, cost and risk associated with the use of that medicine for the therapeutic purpose envisaged. The review is not limited, as the EMA's would be, to the material provided by the manufacturer; nor is the review limited to determining questions of efficacy and safety of that medicine, alone. The national authorities are at liberty to assess the comparative clinical effectiveness (including value for money) of any medicine."
"Can treating clinicians lawfully choose Avastin on grounds of cost?"
Basing their argument on paragraphs 68 to 70 the General Medical Council's guidance that a doctor could only prescribe an unlicensed medicine where there were "medical reasons" for so doing, and that it was "necessary to do so to meet the specific needs of the patient", Bayer and Novartis contended that it was impermissible for a clinician to prescribe an unlicensed drug, on grounds of cost, when a licensed alternative was available. Her ladyship rejected that contention at [151]:
"i) As a matter of construction, paragraph 68 of GMP does not prohibit a clinician from prescribing an unlicensed drug simply because there are licensed alternatives.
a) That paragraph contains guidance indicating in general terms what a doctor "should usually" do. But the guidance, on its face, admits of exceptions.
b) One such exception is expressed in paragraph 68, namely where a doctor considers the prescription of an unlicensed drug to be necessary on medical grounds. But that cannot be taken to be the only possible exception to the general rule. There may be other exceptions too, not spelt out in the guidance.
c) Further, the context in which this case arises is very unusual given the extensive material to show that the cheaper but unlicensed alternative (Avastin) is of equivalent clinical effectiveness and safety as the licensed alternatives. This case is far outside the category of "usual" cases at which paragraph 68 is directed.
ii) Paragraphs 69-70 do not preclude the prescription of unlicensed medicines, simply because there is a licensed alternative available. Specifically, paragraph 69 does not contain a comprehensive list. It is just a list of examples of situations where it "may" be necessary to prescribe an unlicensed medicine. Other situations may exist, which are not on the list.
iii) The GMC guidance, considered overall, positively requires treating clinicians to take cost into account as an element of good medical practice. That obligation does not stop simply because an unlicensed drug is under consideration. Having regard to resources is an enduring requirement, which touches on every decision which a clinician makes."
"i) As a matter of construction, paragraph 68 of GMP does not prohibit a clinician from prescribing an unlicensed drug simply because there are licensed alternatives.
a) That paragraph contains guidance indicating in general terms what a doctor "should usually" do. But the guidance, on its face, admits of exceptions.
b) One such exception is expressed in paragraph 68, namely where a doctor considers the prescription of an unlicensed drug to be necessary on medical grounds. But that cannot be taken to be the only possible exception to the general rule. There may be other exceptions too, not spelt out in the guidance.
c) Further, the context in which this case arises is very unusual given the extensive material to show that the cheaper but unlicensed alternative (Avastin) is of equivalent clinical effectiveness and safety as the licensed alternatives. This case is far outside the category of "usual" cases at which paragraph 68 is directed.
ii) Paragraphs 69-70 do not preclude the prescription of unlicensed medicines, simply because there is a licensed alternative available. Specifically, paragraph 69 does not contain a comprehensive list. It is just a list of examples of situations where it "may" be necessary to prescribe an unlicensed medicine. Other situations may exist, which are not on the list.
iii) The GMC guidance, considered overall, positively requires treating clinicians to take cost into account as an element of good medical practice. That obligation does not stop simply because an unlicensed drug is under consideration. Having regard to resources is an enduring requirement, which touches on every decision which a clinician makes."
Is Avastin safe for ophthalmic use?
Bayer and Novartis argued that it was not safe or at least not as safe as EYLEA and Lucentis and sought permission to call medical evidence in support. The judge did not consider medical evidence to be necessary. There was no suggestion that the CCGs had acted irrationally and they and NICE had already concluded that Avastin was safe.
Her ladyship found on the evidence before her that there was.
Is Avastin an unlicensed medicine or off-label use of a licensed medicine?
Is Avastin an unlicensed medicine or off-label use of a licensed medicine?
The learned judge concluded that Avastin was an unlicensed rather than an off-label medicine but added that the point was not important to her conclusion on the lawfulness of the CCGs' decision.
What is the relevant test by which the lawfulness of the Policy is to be judged, in domestic law?"
Mrs Justice Whipple held that the correct approach in a case such as this must be to ask whether the policy is capable of lawful implementation subject to the rider that the policy would not be lawful if the only method of lawful implementation would be unrealistic. Applying that test the judge considered whether the decision by the CCG could be implemented lawfully - that is to say, whether Avastin could be supplied lawfully by NHS trusts - and decided that it could. Having found against the claimants on every issue, her ladyship dismissed their application for judicial review.
Although this was not an intellectual property case, many of the issues were similar to those that arise in second medical use cases and the arguments were familiar. Anyone wishing to discuss this case or medicines licensing generally should call me on 020 7404 5252 or send me a message through my contact form.
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