All medications must undergo rigorous
testing before they can be approved for use.
The trial process is lengthy and complex and carries significant costs
to the pharmaceutical industry.
Occasionally treatments do not reach the final stages of a trial and
only some receive approval to be marketed.
The various stages are as follows:
1. Developing
and testing a compound in a laboratory
When researchers suspect that a
product or compound may be beneficial, they will first check to see if any
relevant research papers have already been published and will carefully study
any findings.
Often scientists study a particular
illness or symptom in a laboratory and develop a compound with a certain
chemical structure that they believe may provide an improvement or cure. Sometimes new treatments are discovered by
accident or are found to have a use that was not originally envisaged.
2. Pre-clinical
animal testing
Initial tests are carried out in animals, often mice, rats
and occasionally monkeys, to see if the treatment works as predicted. Such tests will also monitor any adverse
effects to other organs, or if the treatment causes illness or
malformation. In the case of tests
relating to Parkinson’s, the condition can be induced in animals by injection
of a compound known as MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine),
a neurotoxin which causes the dopamine
producing cells in the substantia nigra
area of the brain to die as they do in human Parkinson’s.
If pre-clinical tests appear to be safe
and have the desired effect then the treatment company must apply to the
appropriate national or international body for permission to begin human trials
(in the European Union it is the EMA and in the USA the FDA). This formal application will include a study
plan or protocol.
This will detail information regarding any studies that have been
carried out to date, why it is believed that the treatment might be effective
for a particular condition, the anticipated risks and benefits for volunteers,
the eligibility criteria, the process by which volunteers are enrolled (known as informed consent, and
how long the trial should last.
There is usually a review Board made up
of doctors, researchers, consumers (who are often patients) and ethicists. The
Board’s role is to protect volunteers and to ensure that the protocol and
consent process is clear, that the trial is safe and that the likely benefits
outweigh the perceived potential risks. They should complete regular reviews as
the trial progresses to ensure that protocol is being observed.
3. Clinical
trials/testing in humans
Once it has been established that the compound
is safe in animals and permission is granted, testing on humans can begin. Doctors, nurses and other healthcare
professionals will be involved and they will carefully check the health of
participants before they enter the study as well as during and after the trial.
Clinical testing is usually broken down
into four different phases:
- Phase III – if phase II results are positive then the
study is extended to a much larger group in the hope that this will
reinforce findings and show that initial success in the previous phase was
not random. Usually phase III
includes several hundreds or thousands of volunteers, often in a wide range
of countries. The results of this
phase provide more detailed information on the efficacy of a treatment,
the benefits versus risks and optimal dosages for various stages of a
condition such as Parkinson’s.
At this
point the trial usually becomes ‘double-blind’ whereby a number of people
(sometimes known as the experimental group) are randomly chosen to follow a
course of the active treatment. Another
group (known as the control group) are given a placebo or, less
commonly, they may be given either a different dose of the new treatment or a
recognised, standard therapy. It is
double-blind because none of those involved – neither those on the treatment,
nor doctors and researchers – know who is taking the new treatment and who is
in the control group so that their findings cannot be prejudiced in any
way.
At the end
of the agreed testing period - which can last from several months to several
years - the ‘blind’ is lifted and it is revealed who has been taking the new
treatment and who has been following the ‘control’ treatment so that
conclusions can be drawn from the results of this stage of testing. The desirable result is of course that those
on the treatment being trialled have shown more improvement than the other
group of volunteers.
Many placebo
controlled trials have an extension trial which allows all those involved to
have the active treatment if they wish.
Some trials
are also ‘open label’, that is the participants and researchers know what
treatment is being taken and there is no ‘blind’ element to the study.
Whatever
the format of the trial, volunteers are very closely monitored at all times and
tests are carried out, including blood and heart tests. If any safety concerns arise then the trial
may be stopped.
