The principles of controlled clinical trials of drugs.

The principles of evaluation of new drugs are described and discussed. This evaluation is carried out in three consecutive phases. The first one is performed on young, healthy volunteers. The general response to the drug and signs of toxicity are registered. Preliminary data about absorption, elimination and metabolism are collected. The safe dosage range and preferred route of administration are settled. In the second phase, initial trials on a limited number of patients for specific disease control or prophylaxis are carried out. Patients are included in the trial by random selection and stratification. Studies are strictly controlled. To avoid bias, double-blind examination is used in paired patients, a group of patients or by the crossover design. The problems of planning, design of the study, clinical and statistical evaluation of results are discussed. Two examples of controlled clinical studies are given, concerning the assessment of antirheumatic and antianginal drugs. Finally the principles of the third phase of study are discussed. The methods of evaluation described may be applied for the assessment of entirely new substances as well as for verification of the objective therapeutic value of "old" drugs.