Paul Chrisp, Programme Director Medicines and Technologies, NICE
Developing new medicines and then ensuring they are used appropriately is a costly and drawn out process. The NHS needs to make sure that alongside the development of drugs it can optimise the use of existing medicines. The aim being to find more efficient ways to use effective treatments for conditions like cancer, heart disease, Parkinson’s and multiple sclerosis. Discovering new uses for drugs already being used to treat other diseases could offer people more treatment options, improve access and deliver significant healthcare benefits. If a medicine has already been through the regulatory steps to get from the laboratory bench to the patient it may be easier to carry out further research into any added benefits it has and find alternative ways it could be used. As a result, medical research is becoming more interested in how existing medicines can be used to treat other conditions, beyond those they are already licensed for, so-called ‘drug re-purposing’. Many of the medicines where information is emerging about new uses are generic, non-branded ‘off patent’ drugs.
NICE has been part of an important, collaborative project to help speed up the adoption of re-purposed medicines for use in the NHS. After attempts by MPs to bring in new regulations to widen access to off patent use of drugs, ministers saw a growing public desire to tackle the issue. They also recognised that this is a complex problem with many different factors which legislation could not solve. These factors include regulatory process; commercial incentives for manufacturers to stick to single indications; the need for clearer information to support researchers; NHS commissioning and costing pressures; prescribers’ responsibilities for advising patients; and how evidence about re-purposing is used effectively to support clinical decision making.
In 2015 the then Minister for Life Sciences asked the Association of Medical Research Charities (AMRC) to convene a group to explore this issue in more detail, support prescribers’ clinical decisions and improve patient access. Chaired by the AMRC, members of the group included NICE, the Medicines and Healthcare products Regulatory Agency, General Medical Council, pharmaceutical industry, NHS England. Crucially the medical research charities were also well represented including by Breast Cancer Now, Prostate Cancer UK and Parkinson’s UK. Any solutions proposed could not undermine existing regulations for assuring the safety, effectiveness and quality of new medicines used by the NHS. The group therefore looked at how medicines regulation could enable drug re-purposing, where there is strong evidence to support use in patient care and it is felt clinically appropriate. Where research shows benefits of using drugs to treat other conditions, clear advice and support is needed to re-purpose licensed medicines. All the group’s findings and recommendations were published in December 2017 in a report
To help improve patient access and support effective clinical decision making, NICE provides advice on therapeutic use, makes recommendations in our guidelines and raises awareness through our evidence summaries, and via our medicines and prescribing networks. We also provide resources to support shared decision making between doctor and patient, and ensure the British National Formulary includes information on off-label use of medicines.
One example is our 2013 recommendation that women with a family history of breast cancer could be offered preventive treatment with tamoxifen or raloxifen. This marked a major shift in breast cancer treatment, giving women at high or moderate risk of developing breast cancer an alternative to a double mastectomy. At that time, neither medicines were licensed as preventative treatments in the UK although they were approved in the United States after several studies showed they could reduce a person’s risk of developing breast cancer by around a third. Our recommendation broke new ground for the NHS and to support it, we produced a series of decision aids for healthcare professionals to use with patients that outlined the pros and cons of preventative treatment for breast cancer. On the back of taking this action a manufacturer has since sought a variation on its tamoxifen licence from the MHRA to include breast cancer prevention. The variation was approved in April which is good news for breast cancer patients.
The Drug Re-purposing Group’s report features similar forward thinking examples showing how re-purposing can work. Bisphosphonates are licensed to treat osteoporosis and reduce the damage to the bones caused by cancer that has spread there. A Lancet study showed that giving a bisphosphonate to post-menopausal women with primary breast cancer could reduce the risk of it spreading to the bone and other areas of the body and in some cases reduce the risk of dying. NICE provided its own commentary on the Lancet study to raise awareness of the benefits among prescribers and commissioners and provide necessary rigour and reassurance that the decisions clinicians took were the right ones for their patients. For docetaxel, which is used with hormone therapy to treat metastatic prostate cancer, NICE published a rapid evidence review that showed the benefits of having access to the drug earlier. The NICE rapid review was used to inform commissioning of docetaxel by NHS England helping to bring this medicine to more people who need it.
Both of these examples and our guidance around tamoxifen demonstrate the clear cost-effective and life-extending benefits to patients of drug re-purposing. Further research is starting to indicate that there could be many other disease areas and patient groups that could benefit from the use of re-purposed medicines including neurological conditions like multiple sclerosis and Parkinson’s disease. The recommendations in the working group’s report reflect the coming together of all stakeholder opinion, expertise and experience involved in re-purposing off-patent drugs use and medicines regulation. What this important work shows is that when new research comes to light, the system can work together across the medicines life cycle to realise opportunities to enhance medicines uptake, supported by clear evidence of their potential to improve patient care.