CONCENTRATION-CONTROLLED TRIALS - WHAT DOES THE FUTURE HOLD

There can be no doubt that the introduction of measures to control the drug concentration in clinical trials results in additional complexity and increases cost. However, these disadvantages may be balanced by increased study power, a possible reduction in patient numbers and the gain of additional information relating drug concentrations to pharmacodynamics during drug development. Also, the measurement of drug concentrations rationalises the sometimes criticised intention-to-treat analysis,39 by eliminating the non- or poorly compliant patient from the evaluated study data. There is a need to integrate pharmacokinetics and pharmacodynamics during drug development.40 Concentration-controlled studies may be one of the ways to do this, but the few, non phase I studies, which have been completed and published, have involved only compliance checking,41 relatively straight-forward therapeutic drug monitoring19,42,43 or have been undertaken in single centres.16,17,21,44–47 Before the potential benefits of concentration-controlled trials can be realised in a wider arena, the practical problems, such as those discussed in section 3, must be addressed. © 1995, Adis International Limited. All rights reserved.