[Methodology of phase II clinical trials of hypocholesteremic drugs: which criteria?].

Phase II is crucial in drug trials: during this period the first patients are exposed to the drug and the results influence the continuation of the development and the success of later trials. This stage is fundamental in lipid lowering drugs considering the costs of development and potential benefits for public health. The choice of pertinent criteria for the design of a lipid lowering drug trial depends on the analysis of data acquired during previous large scale trials. These criteria should demonstrate the potential of the tested drug and the best conditions of its administration. It is especially at this stage that the drug dosage optimising the efficacy/tolerance ratio should be determined. Analysis of large scale prevention trials indicates LDL-cholesterol as the principal criterion. It is related to coronary risk in the major trials of lipid lowering drugs. A reduction of LDL-cholesterol gives a good numerical estimate of the expected reduction of cardiovascular risk. It is then possible to formulate the hypotheses required for the design of these trials, in particular to calculate the size of the treatment group required. The total cholesterol should also be measured above all because of the large amount of data correlating it with cardiovascular risk. The HDL-cholesterol and triglycerides should also be taken into account even though some of the data concerning these parameters is controversial. The discrimination obtained by measuring HDL-cholesterol is without any doubt crude, and future criteria should enable more accurate and rapid evaluation of lipid lowering activity.(ABSTRACT TRUNCATED AT 250 WORDS)