Draft guidance on clinical trials recognises needs of non-commercial research
BMJ 2004; 329 doi: https://doi.org/10.1136/bmj.329.7459.191-b (Published 22 July 2004) Cite this as: BMJ 2004;329:191
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The draft EU Good Clinical Practice (GCP) Directive is indeed in an
early stage of development and it is hoped that future revisions and
refinements will align the Directive again to the cornerstone document in
clinical research, the ICH Note for Guidance on GCP (E6).
ICH GCP, chapter 2, lists 13 key principles which are considered
fundamental for every clinical trial. As ICH is a 'team effort' of the
three major regulatory areas, Europe - USA - Japan (plus others, of
course), it is difficult to understand that these ICH GCP principles
appear to be made less binding for non-commercial research: "The
conditions under which the non-commercial research is conducted by public
researchers, and the places where this research takes place, make the
application of certain of the principles of good clinical practice
unnecessary or guaranteed by other means."
Is this the first sign of a double standard for clinical trials,
promoting 'GCP light' for academic research? I hope not. Upon close
examination of the 13 ICH GCP principles, I fail to discover opportunities
for making these principles less applicable or even unnecessary for non-
commercial trials. Clinical research is a serious business, and with
lessened standards for academia, transparency of the clinical drug
development process, confidence in the clinical trial data and,
eventually, the safety of the trial participants might be harmed. Not a
desirable outlook!
The challenge is to build GCP-compliant, effective AND efficient
processes for setting-up and conducting clinical trials, for non-
commercial and commercial clinical trials. High-quality research mandates
high-quality procedures.
Competing interests:
None declared
Competing interests: No competing interests
It is disappointing that the comments made by Susan Mayor are so
brief that the reader may draw conclusions that are not representative of
the draft Directive or the underlying regulatory environment.
Although it may be being pedantic, we should recognise that the
document is a draft of a Directive that describes the “… laying down of
principles and detailed guidelines for good clinical practice as regards
investigational medicinal products….” If, or when, the final version of
the Directive is agreed, one anticipates that it will, eventually, become
enshrined in the national laws of the member states, as has Directive
2001/20/EC.
She is wrong to write that the Directive 2001/20/EC was “… [to]
harmonise approval and monitoring of commercially sponsored clinical
research….” Directive 2001/20/EC made no such distinction and nor does the
Statutory Instrument (SI), which sets out the legal requirements with
which clinical research in the United Kingdom must now comply.
Whilst the draft Directive does have some similarities to Directive
2001/20/EC, it represents the first published attempt to formalise the
interpretation of what is “good clinical practice” (GCP) within the
context of medicinal clinical research. With GCP, ICH GCP and the
activities of the WHO in this area, it does seem reasonable that we should
endeavour to produce a harmonised set of definitions of common, high
standard. Even though, the reality is that the differences are not of
great magnitude, and all are focused on the wellbeing of subjects who take
part in medicinal clinical research.
Susan Mayor’s comments on item 11 of the introduction, and others we
have received, seem to have been taken out of context. This statement
seems to be directed towards good manufacturing practice (GMP) aspects, as
twice it refers to “… as far as manufacturing or importation are
concerned….” This statement reflects the concerns that were raised with
respect to the “quality” aspects of investigational medicinal products
(IMPs) referred to in Directive 2001/20/EC, where the need to provide
detailed pharmaceutical data on products with a marketing authorisation
might well be impossible for anyone, other than the manufacturer.
Unfortunately, the draft Directive does lack a certain substance and
invites criticism, even if it is misplaced. We all recognise the vital
role played by those in academic medicinal clinical research, as from such
work we have opportunities to move forward in advancing healthcare for
patients. However, such steps forward must be based on the sound
principles of clinical research (e.g. GCP) with which the industry have
been familiar for many years. There is an underlying and continuous theme
that academic medicinal clinical research is being undermined and/or
disadvantaged by the introduction of first, the Directive and more
recently, the SI. No doubt, the debate will continue, but we must have
total confidence in the data obtained from such research, and this is best
achieved by having administrative and supplementary information that
demonstrate the quality of the research.
Many, I hope most, of us who have been involved in this kind of
research for many years are concerned that a ‘two-tier’ structure might
prevail; the primary reason for this being a view in academia that the new
processes, procedures and documentation requirements are an unnecessary
and unwanted bureaucracy. The high standard of UK medicinal clinical
research must be maintained, and we should continue to raise such
standards in line with the expectations of the wider scientific and
regulatory community. Above all, it is imperative that we maintain and
improve public confidence in all aspects of this research, and the
resulting changes in clinical practice, therapeutics and the availability
of new medicinal products which follow. Being able to demonstrate that the
research was carried out to a high standard of quality is central to
achieving this goal.
If all of this means that all medicinal clinical research should be
conducted to such high standards, is that such a bad objective?
Competing interests:
None declared
Competing interests: No competing interests
Before anyone gets too excited, please note that the EU GCP directive
is NOT a redraft of the EU Clinical Trials Directive. There was some
concern that this new directive on Good Clinical Practice would be even
more proscriptive than the Clinical Trials Directive (which came into
force on 1 May this year), but this has not happened. In fact, the
document is refreshing in the flexible approach it takes, something not
often found in legal documents, particularly those concerned with GCP.
Competing interests:
None declared
Competing interests: No competing interests
Re: 'GCP light' for academia? No double standards, please!
I am a member of an academic working group which exists since more
than 15 years and intends to increase the quality of non-commercial
trials. From my experiences a pragmatic use of the ICH-GCP standards (Good
Clinical Practice standards of the International Conference on
Harmonisation...) really makes sense. However, one of the major problems
is the dramatic increase of formal procederes according to the detailed
guidances of the European Commission. The documents which are now
obligatorily required by the authorities (e.g. application form plus
appended information) are designed especially for commercial trials. In
the case of most academic trials such huge and detailed amount of
information is not necessary. It would be sufficient to provide only very
short basic information to the authorities and to discuss the requirements
of additional specific documents with the competent ethics committee.
For my opinion the cancellation or at least the dramatic reduction of
these overwhelming formal procederes which do not contribute to the
quality of a trial would be more beneficial than the allowance to reduce
quality assurance and quality control. Of course, quality control depends
on the kind of performed trial and - this is at least my interpretation of
GCP - specific and clever adaptations are within the meaning of GCP.
Competing interests:
None declared
Competing interests: No competing interests