The use of animals in drug testing is the subject of considerable debate in the
pharmaceutical industry as well as by the general public. Most countries are
committed to reducing the number of animals used in this way to a minimum
and are actively investigating the use of chemical and other alternative methods.
These methods include avoiding replication of experiments by different countries
centralizing their validation procedures, using human cellin vitrotests instead of
animalin vivotests and eliminiating methods that are not relevant to humans.
However, it is unlikely that it will be possible to replace all animal testing. Once
the drug has passed the preclinical trials it undergoes clinical trials in humans.
These trials can raise legal and ethical problems and so must be approved by the
appropriate legal and ethical committees before the trials are conducted. In most
countries this approval requires the issuing of a certificate or licence by the
appropriate medicine control agency (see section 11.8).
In order to accurately assess the results of a clinical trial, the results must be
compared with the normal situation and so, in the trials conducted on healthy
humans, 50%of the subjects are normally given an inactive substance in a form
that cannot be distinguished from the test substance. This inactive dosage form is
known as aplacebo. Furthermore, the results of a trial must be reliable and not
subject to influence by either the person conducting the trial or the recipient of
the drug. Consequently, it is now common practice to carry out adouble blind
procedure, where both the administrator of the drug and the recipient are
unaware whether they are dealing with the drug itself or a placebo. In addition,
subjects are randomly chosen to receive either the placebo or the drug.
Trials conducted on healthy subjects do not demonstrate the beneficial action
of the new drug. It is necessary to carry out double blind trials on unhealthy
patients to assess its efficacy. However, the use of a placebo with patients who
are ill raises moral and ethical considerations. Placebos may still be used if the
withdrawal of therapy causes no lasting harm to patients. If this is not possible,
the effect of the new drug is compared with that of an established drug used to
treat the medical condition. This reference drug should be carefully selected. It
should not be chosen so as to give the new drug an inflated degree of potency
that could be used to give the manufacturer an unfair commercial advantage
and the patient an inaccurate idea of the medicine’s effectiveness. A third
alternative is to usecross overtrials. Halfway through the trial the patients
receiving the drug are switched to either the placebo or the reference drug and
the patients receiving the placebo or reference drug are given the new drug. This
is ethically more acceptable as both groups have been exposed to the benefits of
the new drug.
The first clinical trials (Phase Itrials) are usually conducted on small groups
of healthy volunteers, which do not include children and the elderly. These
232 DRUG DEVELOPMENT AND PRODUCTION