Comparison of dose-finding designs for narrow-therapeutic-index drugs: Concentration-controlled vs. dose-controlled trials

Clinical Pharmacology and Therapeutics

Volumn 86, Issue 1, 2009, Pages 62-69

  Lledo Garcia R ^a   Hennig, S ^a   Karlsson, M O ^a  

^a UPPSALA UNIVERSITY   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOSUPPRESSIVE AGENT;

ARTICLE; CONTROLLED STUDY; DECISION MAKING; DOSE CALCULATION; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG EXPOSURE; DRUG MONITORING; PRIORITY JOURNAL; SIMULATION;

DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; PHARMACEUTICAL PREPARATIONS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RESEARCH DESIGN;

EID: 67650573198     PISSN: 00099236     EISSN: 15326535     Source Type: Journal    
DOI: 10.1038/clpt.2009.23     Document Type: Article

References (16)

1. Food and Drug Administration. Guidance for Industry. Exposure-response relationships - study design, data analysis, and regulatory applications. (2003). Accessed 6 May 2008.
2. Peck, C.C. The randomized concentration-controlled clinical trial (CCT): an information-rich alternative to the randomized placebo-controlled clinical trial (PCT) [abstract]. Clin. Pharmacol. Ther. 47, 148 (1990).
3. Sanathanan, L.P. & Peck, C.C. The randomized concentration-controlled trial: an evaluation of its sample size efciency. Control. Clin. Trials 12, 780-794 (1991).
4. Holford, N., Black, P. , Couch, R., Kennedy, J. & Briant, R. Theophylline target concentration in severe airways obstruction - 10 or 20 mg/L? A randomised concentration-controlled trial. Clin. Pharmacokinet. 25, 495-505 (1993).
5. Hale, M.D. et al. The pharmacokinetic-pharmacodynamic relationship for mycophenolate mofetil in renal transplantation. Clin. Pharmacol. Ther. 64, 672-683 (1998).
6. Endrenyi, L. & Zha, J. Comparative efciencies of randomized concentration- and dose-controlled clinical trials. Clin. Pharmacol. Ther. 56, 331-338 (1994).
7. Karlsson, K.E., Grahnén, A., Karlsson, M.O. & Jonsson, E.N. Randomized exposure-controlled trials; impact of randomization and analysis strategies. Br. J. Clin. Pharmacol. 64, 266-277 (2007).
8. Lledó-García, R., Hennig, S. & Karlsson, M.O. Infuence of underlying assumptions on evaluating the relative merits of concentration-controlled versus dose-controlled trials. Clin. Pharmacol. Ther. (2009); e-pub ahead of print 11 March 2009.
9. Holford, N., Hashimoto, Y. & Sheiner, L.B. Time and theophylline concentration help explain the recovery of peak fow following acute airways obstruction. Population analysis of a randomised concentration controlled trial. Clin. Pharmacokinet. 25, 506-515 (1993).
10. Cross, J., Lee, H., Westelinck, A., Nelson, J., Grudzinskas, C. & Peck, C. Postmarketing drug dosage changes of 499 FDA-approved new molecular entities, 1980-1999. Pharmacoepidemiol. Drug Saf. 11, 439-446 (2002).
11. Peck, C.C. Postmarketing drug dosage changes. Pharmacoepidemiol. Drug Saf. 12, 425-426 (2003).
12. Sheiner, L.B. Learning versus confrming in clinical drug development. Clin. Pharmacol. Ther. 61, 275-291 (1997).
13. Peck, C.C. & Cross, J.T. "Getting the dose right": facts, a blueprint, and encouragements. Clin. Pharmacol. Ther. 82, 12-14 (2007).
14. Levy, G. Concentration-controlled versus concentration-defned clinical trials. Clin. Pharmacol. Ther. 53, 385-388 (1993).
15. Beal, S.L., Sheiner, L.B. & Boeckmann, A. NONMEM Users' Guides (NONMEM Project Group, University of California, San Francisco, CA, 1996).
16. Lindbom, L., Pihlgren, P. & Jonsson, E.N. PsN-Toolkit - a collection of computer intensive statistical methods for non-linear mixed efect modeling using NONMEM. Comput. Methods Programs Biomed. 79, 241-257 (2005).