Clinical Pharmacokinetics

, Volume 28, Issue 2, pp 93–99 | Cite as

Concentration-Controlled Trials

What Does the Future Hold?
  • Atholl Johnston
  • David W. Holt
Leading Article


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 monitoring[19,42,43] 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.


Maximum Tolerate Dose Suramin Pharmacokinetic Variability External Quality Assessment Scheme Pharmacodynamic Variability 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • Atholl Johnston
    • 1
  • David W. Holt
    • 2
  1. 1.Clinical PharmacologySt Bartholomew’s HospitalLondonUK
  2. 2.The Analytical Unit, Cardiological SciencesSt George’s Hospital Medical SchoolLondonUK

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