A new scheme allows the prescribing of medicines that have not completed full clinical trial testing if they target life-threatening or seriously debilitating conditions, as Richard Hough explains

On April 7, the government launched the non-statutory Early Access to Medicines Scheme (EAMS), which will run alongside existing UK and EU statutory medicines licensing regulations. Under EAMS, patients may be prescribed unlicensed or off-label medicines that might not have undergone full clinical trial testing and which have not been granted marketing authorisations.

Under the existing statutory scheme for medicines regulation, a number of licences must be acquired before a medicine can legally be put on the market in the UK. Firstly, the medicine itself must have a marketing authorisation, which stands as verification that it has met acceptable standards of safety, quality and efficacy. In addition, the companies involved in the manufacture and distribution of the product must have a manufacturer’s or wholesale dealer’s licence. New medicinal products that are still in development also need clinical trial authorisations before they can be tested on humans.

Marketing authorisation

In order for a medicine to obtain a marketing authorisation, the Medicines and Healthcare products Regulatory Agency (MHRA) must evaluate the medicine’s beneficial effects against its possible harmful effects. Evaluation takes into account the nature of the active ingredients, dosage form, condition to be treated, effective dose, type of patient and duration of treatment. A high risk-to-benefit ratio may be acceptable in the treatment of terminally ill patients where quality of life might be enhanced, whereas a very low risk-to-benefit ratio will be required in the treatment of patients with self-limiting diseases, for prophylaxis and chronic illnesses.

However, EAMS will be limited to only those medicines that target life-threatening or seriously debilitating conditions for which there are no existing treatments, or where existing treatments are unsatisfactory. Sufficient quality, safety and efficacy data must be available to convince the MHRA that the risk-to-benefit ratio of the product is positive and that the medicine represents a significant advance in the treatment of an unmet need. Medicines that may be prescribed under EAMS will normally be eligible for an early access scientific opinion after phase III clinical trials, although medicines with exceptional and compelling data may also be eligible after phase II trials.

"New medicines prescribed under EAMS will be made
available free-of-charge by companies
until a marketing authorisation is granted"

The EAMS comprises three main stages:
1. Companies with medicines that meet the above criteria may apply to the MHRA on the basis of either phase II or III clinical trials data for their product to be designated as a ‘Promising Innovative Medicine’ (PIM). This serves as an early indication that the product may be made available under the EAMS.

2. Companies with the appropriate data may then apply to the MHRA for an EAMS scientific opinion. Where the evidence is sufficiently compelling, the MHRA will publish an opinion which is intended to support prescribers in deciding whether to prescribe the medicine on an unlicensed or off-label basis. Following a positive EAMS scientific opinion, the MHRA will publish a public assessment report and the treatment protocol on its website. This will include:
• How the product is to be used
• How it works
• Summary of key clinical studies
• Risks and benefits
• Reason for the positive EAMS scientific opinion
• Any uncertainties
• Information about ongoing clinical studies
• Measures in place to monitor and manage risk.

3. The clinical and cost effectiveness of newly authorised medicines in the UK are generally appraised by the National Institute for Health and Care Excellence (NICE), which issues guidance regarding use of such products. NHS commissioning bodies are under a legal duty to fund products recommended by NICE. The EAMS envisages joint parallel scientific advice meetings between the MHRA and NICE in relation to clinical development programmes for products that go through EAMS, which will provide an opportunity for companies to benefit from early engagement with NICE in order to expedite the commissioning of their product.

Information for prescribers

The ultimate responsibility for deciding whether a patient should receive an EAMS product remains with the prescriber. The intention of the EAMS is to ensure that prescribers have the information they need to prescribe the product in the absence of complete clinical trials data.

New medicines prescribed under EAMS will be made available free-of-charge by companies until a marketing authorisation is granted. In order to comply with legislation that restricts the promotion of unlicensed medicines, companies will not be allowed to draw prescribers’ attention to products that have received a positive EAMS opinion. However, information will be published on the MHRA website and the government has suggested that professional bodies will be instrumental in ensuring that prescribers are made aware of the products.

Pharmacists must ensure that, if presented with a prescription for an EAMS medicine, they refer to the MHRA website so that they can satisfy themselves that they have fulfilled their professional duty to secure the safe and effective supply of such medicines.

EAMS will be available in England, but it is not yet known whether the devolved administrations will participate.

Richard Hough is an associate solicitor and pharmacist at Brabners LLP.

Contact him on 0151 600 3302, or at richard.hough@brabners.com.