The reality of prescribing freedoms in the UK
In 2018, Sir Liam Donaldson, a recognised champion of patient safety and public health, said: “To err is human, to cover up is unforgivable, and to fail to learn is inexcusable.” Doctors face a number of challenges when prescribing related to patients, their own practice and the local health system. In this article, we will outline and explore the complexities of drug approval within the United Kingdom’s National Health Service (NHS) and the main prescribing challenges.
Drug approval and prescribing in the UK is a centralised and complex process. The majority of prescribing in the UK occurs within the NHS. After a pharmaceutical product achieves marketing authorisation from the Medical and Healthcare products Regulatory Agency (MHRA), a Health Technology Appraisal (HTA) submission must be made to the National Institute for Health and Care Excellence (NICE) to receive a recommendation for use – thereby making the drug available to prescribers – within the NHS. Several factors are considered when reviewing a new medicine including clinical, health economic impact and cost-effectiveness. If the government agrees, it provides funding after NICE approval. Subsequently, medicines become available at the primary care and hospital level by introduction into local formularies.
Prescribing challenges – Errare Humanum est, perseverare autem diabolicum
Doctors face major challenges to prescribe safely. The ageing population, increasing complexity (eg, polypharmacy and co-morbidity), coupled with time pressures, are intensifying these challenges. In addition, there are other restrictions within the NHS. Prescribing costs contribute a significant proportion of all expenditure in the NHS, and these costs are rising. Clinical Commissioning Groups (CCGs) currently responsible for planning and commissioning health services locally have an increasing focus on medicines optimisation by, for example, streamlining local formularies, drug switching to more cost-effective options, and scrutinising prescribing considered excessive at a primary care level. Prescribers must therefore balance complex clinical and financial aspects while managing the time constraints of daily practice; concerns have been raised regarding non-payment or financial penalties by CCGs in cases of ‘excessive’ prescribing which adds additional burden and worry for doctors.
High-cost drugs and off-label use
In March 2021, the NHS approved the world’s most expensive drug, Zolgensma (onasemnogene abeparvovec), costing £1.79 million for a single dose, for paediatric patients affected by progressive spinal muscular atrophy (SMA). In the NHS, medicines exceeding £2,000 per annum per patient are ‘high cost’ and subject to strict prescribing guidelines. This illustrates one of the challenges within the system – annual budgeting. If successful, Zolgensma may result in a child enjoying a normal life span, reducing the annualised cost to around £25,000 – still high – but much lower than the headline figure. The use of high-cost drugs is restricted to specialised centres, with the predominant use of biologics in rheumatology, gastroenterology, ophthalmology and dermatology.
If a patient is ineligible per the guidelines, doctors can submit an Individual Funding Request (IFR). This process is often time-consuming. Uncertainty of approval leaves doctors and patients with frustration and may delay treatment. An investigation published in the British Medical Journal found the number of IFRs in England has increased markedly throughout the years. In June 2020, a retrospective study of IFR applications from a tertiary hospital showed a 71% decline rate for NHS England and 34% for CCGs; the primary reason cited was lack of exceptionality. Hence, gaps remain in access to high cost medicines for patients with rare and refractory diseases.
Another method used by doctors is off-label prescribing. This refers to the prescribing of an authorised medicinal product outside the terms of the marketing authorisation, as reflected in the Summary of Product Characteristics. This might include use for a different indication, dosage (or dosage frequency), or patient group (eg, children or pregnant women). Although precise figures are unavailable, it is clear that off-label use is common. This is particularly so in populations rarely studied in drug development programmes, eg, neonates, children, pregnant women and the elderly, and in complex indications such as oncology, infectious disease (HIV/AIDS) and psychiatry. The ultimate responsibility lies with the prescribing physician. If the prescription is for off-label use, the physician’s responsibilities are greater.
Last year, in a judgment considered surprising by many, the UK Court of Appeal ruled that a policy of offering Avastin off-label to NHS patients with wet age-related macular degeneration (AMD) as an alternative to the more expensive, mechanistically-similar AMD drugs Lucentis and Eylea, was lawful. This judgment rejected arguments from the manufacturers that this breached EU law on medicines and UK legislation. Estimates of the saving to the NHS for using Avastin instead of these others range from £200 million to £500 million per year.
This judgment created an interesting conundrum. Data demonstrating the effectiveness of Avastin for AMD was deemed sufficient for twelve CCGs to adopt a policy encouraging its use as the treatment of choice. Given the powers of the CCGs, it seems likely that prescribers in these regions will face significant challenges in prescribing Eylea or Lucentis. Moreover, this judgment creates a precedent. Generic substitution is well established in the UK, but now it appears that drugs which are not patent-expired could be replaced on cost grounds if proven to be similarly effective.
The case also illustrates the geographical restrictions in prescribing. CCGs are free to make their own decisions influencing local formularies, and as a result, a drug available in one region may not be available in an adjacent region. Off-label prescribing is perfectly legal given the principle of therapeutic freedom, but it comes with additional ethical, clinical and legal responsibility for the prescribing doctor.
Doctors walk a fine line between advocating the best treatments for patients while operating within the boundaries and constraints of their individual healthcare systems.
The UK’s NHS, like similar healthcare systems across the world, is under pressure to decrease costs. Doctors already face significant clinical challenges in prescribing safely and have the additional weight of responsibility from an ethical and legal perspective.
However, the additional burden of administrative tasks around prescribing, combined with unrelenting pressure of daily practice, can lead to higher prescribing errors. According to BMJ Quality and Safety, published June 2020, there are more than 237 million medication errors every year in England – the avoidable consequences of which cost the NHS upwards of £98 million and more than 1,700 lives every year. This clearly outlines how cost containment in one area might have a knock-on effect both on doctors and patients.
Everyday clinical decisions are increasingly challenged by other non-clinical staff due to factors described in this article. This can lead to job dissatisfaction and burnout. As a result, the NHS risks losing valuable and highly skilled staff.
With finite resources and growing demand, efforts to increase efficiency in medicines management and prescribing are likely to continue, and with that, a progressive reduction in doctors’ prescribing freedom.
Costanza Evangelio is senior medical director, Pediatrics/Internal Medicine - Medical Affairs, Mayuri Karela, medical director, Rheumatology/Internal Medicine - Medical Affairs, and Harris W. Dalrymple, executive director, Medical & Scientific Affairs, Center for Pediatric Clinical Development, all at PRA Health Sciences