Position Statement on Access to Investigational

Cancer Network Pharmacists’ Forum &
British Oncology Pharmacy Association
Joint Position Statement
Access to Unlicensed Investigational Drugs Outside of Clinical
There are a number of ways by which clinicians can obtain unlicensed drugs outside of clinical
Where patients have clinical needs that cannot be met by licensed medicinal products,
the law allows manufacture and supply of unlicensed medicinal products (“specials”)
subject to certain conditions. The conditions are that there is a bona fide unsolicited
order, the product is formulated in accordance with the requirement of a UK registered
prescriber, the product is manufactured in a facility licensed by MHRA and is for use by
named patients under the prescriber’s personal responsibility.
“Off-label” use of licensed products
Some licensed products are prescribed for unlicensed uses (“off-label”).The prescriber
once again takes personal responsibility for any resulting adverse effects
Expanded access programs (EAP) or compassionate use programmes.
EAP’s are often used to allow continuation of therapy after individuals in clinical controlled
trials have finished their allotted period of treatment or by pharmaceutical companies in the
lag time between study closure and the granting of a licence by the regulatory authorities.
This position statement encompasses the use of an unlicensed medicine through expanded
access or compassionate use programmes – it does not encompass “specials” nor “off-label” use.
Expanded access (compassionate use) programmes EAPs.
The primary intent of an “expanded access” protocol/compassionate use protocol is to provide
access to a new drug for people with a life-threatening or serious disease for which there is no
good alternative treatment and who are not eligible for entry into the relevant clinical trial(s) . A
secondary purpose is to generate additional information about the drug, especially its safety. This
process results in facilitating access to the drug before it is licensed and can be legitimately
promoted and sold. Use of an EAP is legitimate only if clinical investigators are actively studying
the new treatment in well-controlled studies, or all studies have been recently completed or
closed to recruitment. There must be evidence that the drug is an effective treatment in the
patient group to be treated under the EAP and the drug must not expose patients to
unreasonable risks
Over recent years there has been an increase in the number of cancer drugs being made
available for use via an EAP. This raises two key issues:
The management of clinical risks.
Cancer Network Pharmacists Forum & British Oncology Pharmacy Association Joint Position
Statement on Access to Unlicensed Drugs Outside of Clinical Trials, May 2006
EAP’s have the potential to allow a new unlicensed medicine to be introduced into
Network/Trust use, without appropriate clinical and pharmaceutical scrutiny. The
introduction of medicines through these programmes must be subject to the same level of
control through the same process as that applied to all other medicinal products
irrespective of their licensing status, with particular attention being paid to the risks
associated with their use. Consideration must also be given to the fact that, in the
absence of a clinical trial infrastructure, potentially valuable information about the
observed risks and benefits of the drug may go unrecorded.
The management of costs and financial risks.
It is now almost universal practice for manufacturers to make substantial charges for
administrative and supply costs under an EAP. The cost to the NHS is often almost as much
as the anticipated market price of the drug. Off-trial access to investigational interventions
raises serious issues of equity. Access to treatment under EAPs is usually severely limited by
practical and economic constraints. Many cancer networks are attempting to develop unified
network-wide approaches to managing entry of new drugs, commissioning, and the
prioritisation of resources.The use of an EAP has the potential to bypass this process. By
definition drugs available only via an EAP are not (yet) supported by sufficient evidence to
allow robust clinical assessment or prioritisation for funding by Commissioners, Networks and
The UK Cancer Network Lead Pharmacists’ Forum and the British Oncology Pharmacy
Association believe that cancer networks should discourage access to investigational drugs
outside of clinical trials. Access to unlicensed drugs through Expanded Access Programs should
be allowed only in limited circumstances. These circumstances should be defined locally.
In principle, however, we believe that cancer patients for whom licensed drugs offer no further
treatment options should have access to an investigational drug through an EAP provided:
The patient is not eligible for entry into any relevant clinical trial currently open in that
The prescriber believes that the risk/benefit profile of the new therapy is favourable to the
The prescriber takes full responsibility for the use of this medicine for an individual
Before discussion with the patient, the prescriber has discussed the option of the EAP
with the oncology/haematology pharmacist or Trust Chief Pharmacist and has met in full
all relevant requirements of the Trust or network Drug and Therapeutics Committee.
The prescriber explains to the patient/carer that the medicine is not licensed for use, and
the intended benefits and risks of taking the medicine.
Where a patient information leaflet (PIL) is unsuitable or is not available an information
sheet should be produced in accordance with local procedures for the production of
patient information.
The prescriber obtains and records the patient’s consent to treatment before prescribing.
It should also be noted that
Cancer Network Pharmacists Forum & British Oncology Pharmacy Association Joint Position
Statement on Access to Unlicensed Drugs Outside of Clinical Trials, May 2006
Pharmaceutical companies must not enter into any agreement to supply drugs to
individual clinicians. Drug supplies must always be made exclusively via the established
pharmacy department supply chain.
Supplies of drugs must be delivered to the pharmacy department, Drugs must never be
delivered directly to clinicians, clinical nurse specialists or other non-pharmacy staff.
Before initiating the first supply of a drug for a patient under an EAP, pharmaceutical
companies must confirm to the relevant Drug and Therapeutics Committee (D&TC) in
writing, the proposed arrangements (including any costs) for the continued supply of the
drug for any patients who have already started treatment when a licence for the drug is
Pharmaceutical companies must not take participation in an EAP to mean that the Trust/
Network will automatically fund continued use of the drug once licensed.
Once the drug is licensed a full application should be made by the clinician concerned to
the relevant D&TC in order for a full assessment of clinical evidence and financial impact
to be undertaken
Pharmacists obtaining unlicensed drugs should follow the Guidance For The Purchase
And Supply Of Unlicensed Medicinal Products (1) - there should also be local policy and
SOPs for doing this.
In line with the requirements of the Medicines Management Framework and Standards
for Better Health (2,3,4), Trusts should have systems for the managed entry of new
licensed medicines into local health economies and for review of review use of
unlicensed medicines.
References :
Guidance For The Purchase And Supply Of Unlicensed Medicinal Products Notes For
Prescribers And Pharmacists. NHS Pharmaceutical Quality Assurance Committee. Third
Edition June 2004
Standards for Better Health, Department of Health, April 2005
DoH. Medicines Management in NHS Trusts: Hospital Medicines Management
Framework, 2003.
The supply of unlicensed relevant medicinal products for individual patients. MCA
Guidance Note No. 14 (Previously MAL 14) Revised May 2005
Cancer Network Pharmacists Forum & British Oncology Pharmacy Association Joint Position
Statement on Access to Unlicensed Drugs Outside of Clinical Trials, May 2006