M.

clinical trial of new drugs

The aim of an early clinical study of a new compound is to see if the effects seen in animals may
also be seen in humans, and if the way in the which the drug is handled by human corresponds to that in
animals. Toxicology studies must also be performed to examine the effect of the drug on standard
haematological and biochemical indices. Such early studies will usually be performed in volunteers but
with some agents such as cytotoxic drugs it will be necessary to do these studies in patients with the
disease for which the drug was designed.

Once the initial studies have been performed in man, it will be necessary to conduct more
formal clinical trials. The formal clinical trial is a most powerful tool for the investigation of new drugs,
but in some situations this type of study may be too rigid and unsuitable (e.g if the rate of onset of a
drug’s effect is being studied). Before a clinical trial is mounted, it is important to establish its real
purpose. The aim should be to answer one precisely framed question. it is all to easy to attempt to
design a trial which asks a number of questions, such as is the drug effective? In what patients should it
be used? What is the most appropriate dosage? And how does it compare with other drugs? Such a trial
will fail because it will become to complicated to perform. The comparative clinical trial should be
carried out in equivalent groups of patients who are as closely matched for important variables (e.g. age,
sex, severity of disease, ate) as possible. Although in initial clinical trials, controls may not be needed.
(i.e the study is an open one) it is important to introduce control observations as soon as possible in the
study programme. Thus patients receiving no treatment, or receiving a matching placebo. However,
most commonly the new compound will be compared with a drug that is considered to be the standard
treatment for the disease under study at the time. Thus, for example a new beta-adrenoceptor blocking
drug may be compared with placebo to show that it lowers blood pressure in hypertensive patients, or
with an existing beta blocker to see if it is more (or less) effective than that drug. Historical retrospective
controls are rarely satisfactory. In some situation it may be unethical to withhold active treatment from
the control group of patients and this situation placebo should not be given. Usually the two treatments
are studied in comparable patients over the same period of time. It will be necessary to ensure that
enough patients are included to minimize any inter-patient variability. When the variability between
individuals is a cause for concern, it is often useful to use each patient as his own control, but this can
only be done if the disease is stable. Here all patients are exposed to each treatment in a crossover
design and it is important to ensure that each treatment both precedes and follows each other
treatment the same number of times. This will minimize any “carry-over” effect from one treatment to
the next. In a crossover design if “carry over” is a problem it maybe useful to include a placebo
”washout” period between two active periods. It is important to realize that placebo treatment is not
synonymous with no therapy. Although the placebo will not contain a pharmacologically active agent,
may have measurable effects. About 30 per cent of patients develop side-effects on placebo therapy,
and in many clinical situations the placebo may have therapeutic effects too.