Geoffrey Guy discusses prescribing unlicensed medicines and the Medicines Act
Over the past decade there's been a gradual decline in the prescribing of unlicensed medicines either as part of early exploration of drug efficacy and safety or as individual treatments for patients in whom all other therapies have failed. This decline has for the most part gone unnoticed.
The Medicines Act is clear on the rights of individual physicians to prescribe, on their own responsibility, unlicensed medicines or medicines off label – where such prescribing is warranted on clinical grounds.
This decline in early exploration with unlicensed medicines is not a result of regulatory changes nor the implementation of European clinical research directives but a cultural shift in the attitudes and confidence of the younger generation of clinicians working within the NHS. Many clinicians have reported in general that initiating and carrying out clinical research within the NHS and the trust hospitals is hampered by excessive bureaucracy; but more specifically in the last 12 to 18 months they found that drugs and therapeutics committees in hospitals have banned them from prescribing unlicensed medicines.
The notion that such bans arise from fear of cost or vicarious liability considerations is a real one. The unintended consequence or side effects of such bans has been to diminish very early evaluation of exploratory medicines, which for decades has formed a fundamental and essential part of the initial tentative steps of drug discovery
A recent case highlights the loss of international competitiveness that the UK, a previous world leader in the field, now suffers in clinical research and drug development.
In the autumn of 2012 we were approached by an American family and their physician about a child with drug resistant epilepsy. The physician had heard of the potential benefits of cannabidiol (CBD) in such cases and requested that GW Pharmaceuticals provide cannabidiol that had been under preclinical research as an anti-epileptic agent from number of years.
Cannabidiol is a cannabinoid derived from the cannabis plant and is therefore considered as a schedule one (aka controlled) substance in the United States. As it may have taken some time to obtain the appropriate import permit it was decided to bring the young child to London to be evaluated and if appropriate treated at Great Ormond Street by a world renowned specialist in paediatric epilepsy.
CBD is one of the two major components of a medicine now approved in 25 countries for the treatment of spasticity in multiple sclerosis. Whilst over 20,000 patient years of safety data had been accumulated in adults CBD had not up to that time been administered to children nor infants. Following prescription of CBD by the specialist as an unlicensed medicine for the child over a 13 day period the daily seizure rate dropped from approximately 80 to nearly zero by the time the child returned to the United States.
On hearing of this single case validation of previous anecdotal reports and findings, a number of senior paediatric epileptologists in the United States convened a meeting in New York within one month of the child returning. Within a few months following that meeting the Food and Drug Administration (FDA) granted permission for the child's physician to prescribe Epidiolex (CBD) in the United States. Following this, five leading paediatric epilepsy centres in the US received permission from the FDA to prescribe the medicine for over 125 of their patients as part of an Expanded Access Programme (for unlicensed medicines) and more recently further centres have received permission to prescribe bringing the total in the coming months to over 300 children.
Meanwhile in the UK the specialist at Great Ormond Street received enquiries from the UK and other parts of the world to treat children in the same fashion but was banned from doing so by the hospital's drugs and therapeutics committee on the grounds of insufficient evidence of safety and efficacy in children. This was despite the fact that at that time the FDA had already granted the permission to prescribe Epidiolex as an unlicensed medicine for over 125 children from age 12 months to 18 years.
In the coming months over 300 American children will have received Epidiolex and to date not a single British child has had the product prescribed.
Plans are now well advanced to carry out formal regulatory trials in United States and also to extend the trials into the UK where children suffering with extremely severe forms of epilepsy will at last have the chance receive Epidiolex and give their treating physicians the opportunity to assess its benefits.
It remains to be seen whether the UK’s new Early Access Scheme will actually benefit drugs, such as Epidiolex, and see them delivered to patients faster.
Dr Geoffrey Guy is the founder of GW Pharmaceuticals and has served as Chairman since 1998. Dr. Guy has over 30 years of experience in medical research and global drug development, and was appointed as Visiting Professor in the School of Science and Medicine at the University of Buckingham in July 2011. This speech was originally delivered at the Empower: Access to Medicine Parliamentary Reception on 25th March 2014.