The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has
launched a Notification Scheme for selected clinical trials as part of
a joint project with the Department of Health (DH) and the Medical
Research Council (MRC) on risk-adapted approaches to trial management.
The Scheme may be used for clinical trials involving medicinal products
authorised in any Member State of the European Union, where these
trials:
- relate to the currently licensed range of indications, dosage and product form;
- involve off-label use, where this use is “established practice and
supported by sufficient published evidence and/or guidelines”.
Placebo-controlled trials will not be eligible for the Notification
Scheme, nor will trials in which the marketed product has been modified
- for example, through over-encapsulation. The scheme will apply,
though, in the case of repackaging and/or relabelling of marketed
products.
14-day timeline
Once the MHRA has received a valid notification submission, sponsors
will be sent an acknowledgement letter informing them that the trial
may go ahead 14 days after receipt of the notification, providing the
MHRA has not raised any objections.
If the agency does raises any objections, the submission will be
treated as a standard request for clinical trial authorisation and an
assessment carried out in the usual manner, with a time line of 30 days
from the receipt of the original notification.
“A risk assessment based on the potential risks associated with the use
of the investigational medicinal product should be made by the
sponsor,” the MHRA states. Background documentation on how to do this
is provided on the agency’s website as part of a new section on the
Notification Scheme.
Joint project
The Scheme is the first initiative under the MRC/DH/MHRA Joint Project
on Risk Adapted Approaches to the Management of Clinical Trials of
Investigational Medicinal Products. The second part of the project will
involve guidance on risk-proportionate approaches to the management and
monitoring of clinical trials.
The risk-stratification project was initiated by an ad hoc working
group co-chaired by Professor Janet Darbyshire director of the MRC’s
Clinical Trials Unit, and Professor Kent Woods, chief executive of the
MHRA.
The working group includes representatives of academic researchers and
research governance managers, medical charities, the DH and the
licensing authority.
As a paper drawn up by the working group points out, the current
regulatory framework for clinical trials in the UK and the EU “allows
for a range of risk-adapted approaches that may simplify the processes
for initiating and conducting” some trials.
These adaptations “are largely related to how much is known about the
investigational medicinal product (IMP)”, it adds. The paper proposes a
simple three-tiered risk categorisation approach, based on the
marketing status of the IMP and standard medical care.
GCP concerns
The European Union’s Clinical Trials Directive, 2001/20/EC, makes
compliance with the principles of Good Clinical Practice (GCP) a legal
requirement for everyone in the EU involved in the conduct of any
clinical trial with a medicinal product, the paper observes.
While the Directive recognised that there are commercial and
non-commercial sponsors of clinical trials, “it made no distinction
between them with regard to the GCP requirements”, the working group
adds.
The European Commission has proposed, and consulted on, ‘specific
modalities’ guidance for non-commercial trials to indicate where
certain aspects of GCP could be relaxed for these particular studies,
the paper notes. However, the guidance has never been published.
This vacuum has contributed to non-commercial trialists, and in
particular sponsors of non-commercial research, believing that they
“must manage all aspects of trial conduct and GCP in a similar way to
commercial sponsors”, the working group says.
As a result, and despite there being a degree of flexibility in how the
principles of GCP can be applied, “many organisations have had concerns
about not meeting all of the statutory requirements for the conduct of
clinical trials”.
In turn, the paper adds, some organisations, and particularly those
operating in the public sector, have become reluctant to participate in
clinical trials, while others have taken a risk-averse approach
requiring “additional processes which have increased the cost and
complexity of clinical trials unduly”.
