Advertisement

Concentration-Controlled Trials: Basic Concepts, Design, and Implementation

  • Lilly P. Sanathanan
  • Carl C. Peck

Abstract

A Concentration-Controlled Trial (CCT) is one where subjects are assigned to predetermined levels of average plasma drug concentration. These target concentrations are achieved (within reasonable ranges) by an individualized pharmacokinetically (PK) controlled dosing scheme. In a recent paper (Sanathanan and Peck, 1991), we have investigated the sample size efficiency of the Randomized CCT (RCCT) design in comparison to the traditional Randomized Dose-Controlled Trial (RDCT). We have pointed out that in addition to safety concerns which strongly suggest the use of CCTs for drugs with narrow therapeutic windows, sample size considerations favor the choice of CCTs in many situations. In particular, substantially smaller sample sizes are possible with CCTs which are designed to minimize the interindividual PK variability within comparison groups and consequently decrease the variability in clinical response within these groups. In a subsequent paper (Sanathanan and co-workers, 1991), we proposed a Phase II randomized concentration-controlled titration design with the objective of streamlining the drug development process. In this chapter we present a brief overview of the basic concepts underlying the design and implementation of CCTs.

Keywords

Narrow Therapeutic Window Intrasubject Variability Steady State Average Concentration Individualize Pharmacokinetically Drug Information Journal 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Peck, C. C. (1986). Bayesian pharmacokinetics. Evolution and start of the art. In Young, Ingalls, and Hawkins (Eds.), Simulation at the Frontiers of Science. Eastern Simulation Conference, Norfolk, Virginia. Soc. Comp. Sim., San Diego. pp. 17–20.Google Scholar
  2. Peck, C. C. (1990). The randomized concentration-controlled clinical trial: an information-rich alternative to the randomized placebo-controlled clinical trial. Clin. Pharmacol. Ther., 47, 126.Google Scholar
  3. Peck, C. C., D. Z. D’Argenio, and J. Rodman (1991). Analysis of pharmacokinetic data for individualizing drug dosage regimens. In W. E. Evans, J. J. Schentag and W. J. Jusko (Eds.), Applied Pharmacokinetics 3rd ed. Applied Therapeutics, Inc. Vancouver, Washington. Chapter 3.Google Scholar
  4. Peck, C. C., D. P. Conner, and M. G. Murphy (1989). Bedside Clinical Pharmacokinetics: Simple Techniques for Individualizing Therapy. Applied Therapeutics, Inc. Vancouver, Washington.Google Scholar
  5. Sanathanan; L. P., and C. C. Peck (1991). The randomized concentration-controlled trial: an evaluation of its sample size efficiency. Controlled Clinical Trials, 12, 780–794.Google Scholar
  6. Sanathanan, L. P., C. C. Peck, R. Temple, R. Lieberman, and G. Pledger (1991). Randomization, PK-controlled dosing, and titration: an integrated approach for designing clinical trials. Drug Information Journal, 25, 425–431.Google Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Lilly P. Sanathanan
    • 1
  • Carl C. Peck
    • 1
  1. 1.Food and Drug AdministrationRockvilleUSA

Personalised recommendations