Multicentre
trial checklist
Single Centre
Advantages
Single centre trials are usually set up in a particular hospital,
clinic
or general practice. They are usually small-scale studies,
cheaper
to conduct than multicentre trials and therefore generally easier to
obtain
funding for. Single centre trials provide the flexibility of
approach
necessary for clinicians and scientists to develop new treatments and
can
provide an important source for new therapeutic ideas. In a
single
centre trial the clinical investigators are often continuously involved
and
maintain enthusiasm throughout.
Problems and solutions
Many single centre trials often recruit too few patients to be
scientifically
viable. A trial with only a small number of participants carries
a
considerable risk of failing to demonstrate a treatment difference when
one
is really present i.e. type II error. Often a single source of
participants
may be insufficient to make a clinical trial of viable size. This
problem
may be clear-cut from the beginning but on other occasions it may
linger
on with too few participants and finally peter out as enthusiasm
wanes.
Thus, it is important to recognise early on whether a single centre
trial
is feasible and scrutinise the ethics, organisation and relevance of it
carefully.
Multicentre trials
Advantages
Multicentre trials are carried out for two main reasons. Firstly,
a
multicentre trial is an accepted way of evaluating a new technology
more efficiently; under some circumstances, it may present
the
only practical means of accruing sufficient subjects to satisfy the
trial
objective within a reasonable time frame. Multicentre trials of
this
nature may, in principle, be carried out at any stage of clinical
development.
They may have several centres with a large number of subjects per
centre
or, in the case of a rare disease, they may have a large number of
centres
with very few subjects per centre.
Secondly, a trial may be designed as a multicentre (and
multi-investigator)
trial primarily to provide a better basis for the subsequent
generalisation
of its findings. This arises from the possibility of recruiting
the
subjects from a wider population and of delivering the technology in a
broader
range of clinical settings, thus presenting an experimental situation
that
is more typical of future use. The involvement of a number of
investigators
also gives the potential for a wider range of clinical judgements
concerning
the value of the technology. Such a trial would be a confirmatory
trial
in the later phases of technology development and would be likely to
involve
a large number of investigators and centres. It might sometimes
be
conducted in a number of different countries in order to facilitate
generalisability
even further.
Problems and solutions
Multi-centre trials are considerably more complex (e.g. co-ordination,
quality
control, data management) than single center trials and therefore it is
essential
to have efficient central co-ordination of all trial activities (see
Trial
co-ordination). They are also very expensive to run both in
terms
of
personnel and resources and therefore require adequate funding form the
onset.
If a multicentre trial is to be meaningfully interpreted and
extrapolated,
then the manner in which the protocol is implemented should be clear
and
similar at all centres. Furthermore, the usual sample size and
power
calculations depend upon the assumption that the differences between
the
compared treatments in the centres are unbiased estimates of the same
quantity.
It is important to design a common protocol and to conduct the trial
with
this background in mind. Procedures should be standardised as
completely
as possible. Variation of evaluation criteria and schemes can be
reduced
by investigator meetings, by the training of personnel in advance of
the
trial and by careful monitoring during the trial. Good design
should
generally aim to achieve the same distribution of subjects to
treatments
within each centre and good management should maintain this design
objective.
Finally, one particular difficulty is to motivate all participants in a
large
multicentre trial to play an enthusiastic and responsible role.
In
this respect, collaborator meetings, regular newsletters and feedback
of
general information on the trial’s progress may help (see Sources or
methods
of recruitment).
It is worth noting that the key to a successful multicentre trial is
trial
management (see Trial
management
). Trial managers typically require a range of skills and are
crucial
to the successful running of a trial. He or she may be required
to
spend up to 50% of their time communicating with or traveling to the
outlying
centres.
Multicentre
trial checklist
This checklist has been modified from a checklist prepared for the International Conference on Harmonization Guideline for Good Clinical Practice (ICH GCP)