About research
- Design of clinical trials for anti-epileptic
drugs workshop
Modern trials of new drugs are required to
follow a very strict set of rules in order
to produce good evidence that the new drug
works. Trials that are "randomised, controlled
and double-blind" are considered to provide
the best level of evidence for the efficacy
of a new drug.
Controlled trials are those in which
a "control group" of patients
are enrolled: these do not receive the new
drug and often take a placebo ("dummy
drug") instead. The placebo is usually
in exactly the same form as the real thing,
whether tablet, syrup or injection, and
contains exactly the same ingredients except
the active ingredient. This means that the
difference in treatment between control
and non-control groups is only in the presence
or absence of the active ingredient, and
this allows doctors check more clearly what
its effect is.
Randomised trials are those where
patients enrolling in the trial are allotted
randomly to receive either the trial drug
or placebo. This ensures that the groups
of patients being compared are as alike
as possible, so that differences in the
ages, sex or epilepsy types of the patients
don't skew the results.
Blinded trials are those where the
patients do not know whether they're taking
the trial drug or the placebo (called a
"single-blind" trial) or where
neither the doctor nor the patient knows
this, and only the trial administrators
do (called a "double-blind" trial).
This cuts out any possible psychological
effects of being treated versus not being
treated.
However, ethical considerations must be
taken into account too, and these are especially
important with epilepsy treatments. Generally,
giving a placebo on its own to patients
with damaging seizures is considered unethical
(as it could worsen their epilepsy) so trials
of new anti-epileptic drugs are usually
"add-on" trials, where the new
drug is given in addition to existing medication.
However here, there is a possibility that
interactions between the medications could
skew the results.
Once a drug has been shown to be effective,
then new trials comparing its efficacy to
that of established drugs are carried out.
However these trials do not include a comparison
to placebo, so their conclusions can sometimes
be difficult to interpret.
Additionally in epilepsy, drugs can have
different efficacies depending on the seizure
types or epilepsy syndrome the patient has,
the severity of syndrome and its responsiveness
to drug therapy. This adds another layer
of complexity to assessing a new drug's
efficacy.
The design of clinical trials for anti-epileptic
drugs is therefore very difficult. The aim
when designing one is always to get good
evidence for how well a new drug works,
and in which patients, with the minimum
risk of doing harm. The Epilepsy Research
Foundation (now Epilepsy Research UK) organised
an international meeting to discuss these
issues in September 2000. Thirty-five experts
from a number of European countries and
the USA participated, together with representatives
from the pharmaceutical companies who had
sponsored the workshop.
