The influence of a drug on one or more well defined parameters can be studied by different types of trials which require a more or less large number individuals selected according to inclusion criteria, specific to each study.
Non comparative trial
A trial is not comparative or not controlled when the evaluation of the parameters of the patients treated by the drug under investigation is not compared with that of another group receiving a placebo or a drug of reference.
However, actually, one compares the evolution of the parameters after administration of a drug with the known or supposed evolution in its absence. The spontaneous evolution of pulmonary tuberculosis before 1950 was sufficiently obvious for detecting the beneficial effect of isoniazid without a control group. The frequency of the ruptures of the Achilles tendon in patients treated by fluoroquinolones appeared sufficiently high compared to that which was spontaneously observed for suspecting and then confirming their involvement in this undesirable effect. These two examples show that behind apparently intuitive conclusions hide procedures of analysis of the logical type.
The evolution of the parameters of the treated group is compared with that of a placebo group or that of a group treated with a drug of reference, according to various conditions.
A placebo is a preparation without active product but identical by its aspect to that of a supposed active preparation. The intake of a placebo which should not induce any modification, very often gives either an improvement, at least transient, of certain symptoms, or some adverse effects, headache or asthenia for example. The placebo effects on a drug depend much on the conditions under which it is given.
A placebo-controlled trial is acceptable only for a benign disease for trying to reduce the duration or the symptoms or for a severe disease against which no effective cure is yet known.
When studying a drug in clinical pharmacology, it is necessary to eliminate the part of placebo effect to evaluate the properties of drug objectively but, in therapeutic practise, placebo effect often takes part in the improvement of the patient and is to be sought.
Versus a reference drug
Very often, the effects of a new drug are compared with those of a drug of reference, recognized effective in the indication. For example, a new antihypertensive can be compared with another antihypertensive recognized effective in therapeutics.
Different conditions of comparison tests
- Randomized trial
A trial is randomized when the distribution of the subjects, which satisfy the criteria of inclusion, in the control and treated groups is made by chance, i.e. randomly.
- Open trial
A trial is open or nonblinded when the patients and the investigators know the type of drug the patients are treated by.
- “Blind” trial
A trial is single-blind when only the treated patients are unaware of which type of treatment they receive, studied drug, placebo or drug of reference.
A trial is double-blind when both the patients and the investigators are unaware of the treatment each group is receiving. The studied products have a code name whose correspondence will be disclosed only at the end of the trial.
- Parallel or sequential trial
The essay is parallel when two different groups of patients take part simultaneously in the trial. The trial is sequential when the same group of patient receives first the treatment A and then the treatment B, or conversely.
- Monocenter or multicenter trial
When only one centre, a hospital service for example, carries out the trial, this one is monocentre; but often only one centre is not able to find a sufficient number of patients responding to the inclusion criteria, and several centres following the same protocol are needed and the trial is multicenter; the trial can be regional, national or international.
- Case-control study
For studying, often in retrospective manner, the influence of a drug on the frequency of an event (beneficial or adverse effect), epidemiologic studies are used. These studies are always comparative: the frequency of the event (mortality, cardiovascular accident, cancer…) in the group treated by the drug under investigation, is compared with the frequency of the same event in an identical group but not treated by the drug,. The quotient of the two frequencies, is the odds ratio.
In animal pharmacology, the use of controlled trial is the rule: the product studied is generally compared with the placebo (generally the solvent or the excipient in which the dug is prepared) and with a reference product.
In clinical pharmacology, double-blind randomized trials are most frequent.