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Computer-guided concentration-controlled trials in autoimmune disorders

McMichael, J and Lieberman, R and Doyle, H and McCauley, J and Van Thiel, D and Thomson, A and Fung, J and Starzl, TE (1993) Computer-guided concentration-controlled trials in autoimmune disorders. In: UNSPECIFIED UNSPECIFIED, 510 - 513. ISBN UNSPECIFIED

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A randomized concentration-controlled clinical trial (RCCCT) is an alternate experimental design to the standard dose-controlled study. In a RCCCT, patients are randomly assigned to predefined plasma or blood drug concentration ranges (low, medium, and high). With the caveat that concentration ranges are sufficiently separated, this design should enhance the ability to discover important concentration response relationships. FK-506, a potent and promising immunosuppressive agent for prevention and treatment of graft rejection, has shown significant clinical activity in some immune-mediated disorders. To implement the RCCCT design, a novel FK-506 intelligent dosing system (IDS) was used to guide all doses to prospectively achieve the target concentration range specified in the study protocol. Patients enrolled in these trials suffered from a variety of autoimmune disorders, including multiple sclerosis, primary biliary cirrhosis, psoriasis, autoimmune chronic active hepatitis, and nephrotic syndrome. We observed excellent predictive performance of the IDS for all patients. The accuracy (mean prediction error) of the IDS was −0.022 ng/ml and the precision (standard deviation of the prediction error) was 0.119 ng/ml. Thus, the IDS is both accurate and reproducible for autoimmune patients. We conclude that the RCCCT design, guided by an accurate and precise IDS, is an informative and cost-effective approach for evaluation of efficacy and safety of effective but highly toxic agents. © 1993 Raven Press, Ltd., New York.


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Item Type: Book Section
Status: Published
CreatorsEmailPitt UsernameORCID
McMichael, J
Lieberman, R
Doyle, H
McCauley, J
Van Thiel, D
Thomson, A
Fung, J
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1993
Date Type: Publication
Journal or Publication Title: Therapeutic Drug Monitoring
Volume: 15
Number: 6
Page Range: 510 - 513
DOI or Unique Handle: 10.1097/00007691-199312000-00010
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0163-4356
Other ID: uls-drl:31735062125749, Starzl CV No. 1618
Date Deposited: 08 Apr 2010 17:27
Last Modified: 02 Feb 2019 13:57


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