NHS CCG's Off-Label Bevacizumab Policy Upheld: Comprehensive Commentary on Bayer Plc v. NHS Darlington CCGs

Introduction

The case of Bayer Plc v. NHS Darlington Clinical Commissioning Groups (CCGs) & Ors ([2018] EWHC 2465 (Admin)) presents a significant legal examination of the boundaries between European Union (EU) regulations and national health policies within the United Kingdom (UK). In this High Court judgment, Bayer and Novartis Pharmaceuticals UK Ltd challenged the legality of a policy adopted by twelve Clinical Commissioning Groups (CCGs) regarding the treatment of Age-related Macular Degeneration (AMD), specifically the use of bevacizumab (Avastin) as a preferred treatment option over licensed alternatives like Eylea and Lucentis.

The central dispute revolves around whether the CCGs' policy, which favors the cost-effective, off-label use of Avastin for wet AMD, is lawful under both EU and UK domestic law. The Claimants raised four primary grounds for their challenge, questioning the legal foundation, the compliance with EU directives, patient access to recommended treatments, and the accuracy of informational materials accompanying the policy.

Summary of the Judgment

After a thorough examination of the arguments and relevant legal frameworks, the High Court concluded that the CCGs' policy is lawful. The court dismissed all four grounds of challenge, affirming that:

The European Medicines Agency (EMA) does not possess exclusive competence over the clinical effectiveness and safety assessments of medicinal products for specific uses.
Clinicians are permitted to consider cost-effectiveness when prescribing, especially when licensed alternatives are equivalent in efficacy and safety.
Bevacizumab (Avastin), when compounded for ophthalmic use, is classified as an unlicensed medicine, but national health authorities retain the competence to determine its use based on clinical and economic considerations.
The policy does not undermine the objectives of EU directives or the guidelines established by the National Institute for Health and Care Excellence (NICE).

The judgment emphasizes the autonomy of national health bodies in making cost-effective decisions while adhering to overarching EU regulations designed to safeguard public health.

Analysis

Precedents Cited

The judgment references several key cases that shape the legal landscape concerning the use of medicinal products:

Apozyt AB v Apoteket Farmaci AB: Clarified that compounding processes that do not alter the medicinal product's composition do not require a new marketing authorization.
AG J 'skinen (AGCM): Affirmed that legitimate off-label use of a medicine with existing authorizations is permissible and does not infringe EU law.
R (Rogers) v Swindon NHS PCT: Established that CCGs can have policies on funding specific treatments, provided they meet legal standards.
Commission v Poland (C-185/10): Reinforced that EU directives must be strictly interpreted, especially derogations, to not undermine public health objectives.
Case C-535/11 Novartis Pharma GmbH v Apozyt GmbH: Further supported that repackaging without modification does not constitute a new placing on the market.

Legal Reasoning

The court's reasoning hinged on delineating the competences between EU regulatory bodies and national health authorities. It established that:

EU vs. National Competence: The EMA is responsible for initial marketing authorizations but does not oversee all aspects of clinical effectiveness or budgetary decisions made by national entities like NICE and CCGs.
Off-Label Use: The use of Avastin for ophthalmic purposes, while off-label, does not violate EU directives as long as it does not necessitate a new marketing authorization. National bodies are empowered to assess and approve such uses based on local clinical and economic factors.
Cost Considerations: National bodies like CCGs have a mandate to use resources efficiently, which includes factoring in the cost-effectiveness of treatments. This aligns with both NHS principles and legal obligations under the National Health Service Act 2006.
Lack of Exclusive EMA Competence: The court rejected the Claimants' assertion that EMA has exclusive authority to determine the clinical effectiveness of Avastin for wet AMD, affirming that national bodies have substantial leeway in such assessments.

Impact

This judgment sets a precedent reinforcing the authority of national health bodies in the UK to make cost-effectiveness decisions concerning the use of medicinal products, even when such use is off-label. It clarifies that:

National authorities can implement policies that favor cost-effective treatments without breaching EU directives, provided they do not undermine public health objectives or patient safety.
Clinicians retain the discretion to consider cost alongside clinical effectiveness when prescribing treatments, promoting rational and sustainable use of NHS resources.
The classification of compounded medicines as unlicensed does not inherently render their use unlawful, allowing for flexibility in treatment options within the regulatory framework.

Future cases involving off-label use of medicines will likely refer to this judgment to balance cost-effectiveness with regulatory compliance and patient care standards.

Complex Concepts Simplified

Off-Label vs. Unlicensed Use

Off-Label Use: Refers to using a medicinal product for an indication, dosage, or patient population that is not specified in the product's official marketing authorization. This practice is legal and common, allowing clinicians to use their judgment based on clinical evidence and patient needs.

Unlicensed Use: Occurs when a medicinal product is used without any marketing authorization in a Member State. This typically involves compounding medicines for individual patients or preparing them in ways not covered by any existing authorization. Unlicensed use has stricter regulatory oversight to ensure patient safety.

Compounding

Compounding involves preparing personalized medication by altering the form, dosage, or other aspects of a drug to meet the specific needs of a patient. In this context, compounding Avastin for ophthalmic use entails repackaging it into smaller doses suitable for intravitreal injection.

Clinical Commissioning Groups (CCGs)

CCGs are statutory bodies within the NHS in England responsible for planning and commissioning (buying) healthcare services for their local area. They make policies and decisions regarding which treatments and services to fund, balancing clinical effectiveness with cost considerations.

Conclusion

The High Court's decision in Bayer Plc v. NHS Darlington CCGs underscores the significant role of national health authorities in determining the most cost-effective and clinically appropriate treatments within the NHS framework. By affirming the legality of the CCGs' policy to prefer off-label Avastin based on cost-effectiveness, the judgment provides a clear pathway for integrating economic considerations into healthcare decision-making without undermining patient care or regulatory compliance. This case serves as a pivotal reference for future disputes involving the off-label use of medications and the autonomy of national bodies in managing healthcare resources.