Computer-guided concentration-controlled trials in autoimmune disorders

John McMichael, R. Lieberman, Howard Doyle, J. McCauley, D. Van Thiel, A. Thomson, J. Fung, T. E. Starzl

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)510-513
Number of pages4
JournalTherapeutic Drug Monitoring
Volume15
Issue number6
StatePublished - 1993
Externally publishedYes

Fingerprint

Intelligent systems
Randomized Controlled Trials
Tacrolimus
Autoimmune Hepatitis
Biliary Liver Cirrhosis
Poisons
Immune System Diseases
Graft Rejection
Nephrotic Syndrome
Chronic Hepatitis
Immunosuppressive Agents
Psoriasis
Multiple Sclerosis
Research Design
Grafts
Design of experiments
Safety
Costs and Cost Analysis
Blood
Plasmas

Keywords

  • Autoimmune diseases
  • Concentration-controlled artificial intelligence
  • Dynamic dosing

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Public Health, Environmental and Occupational Health

Cite this

McMichael, J., Lieberman, R., Doyle, H., McCauley, J., Van Thiel, D., Thomson, A., ... Starzl, T. E. (1993). Computer-guided concentration-controlled trials in autoimmune disorders. Therapeutic Drug Monitoring, 15(6), 510-513.

Computer-guided concentration-controlled trials in autoimmune disorders. / McMichael, John; Lieberman, R.; Doyle, Howard; McCauley, J.; Van Thiel, D.; Thomson, A.; Fung, J.; Starzl, T. E.

In: Therapeutic Drug Monitoring, Vol. 15, No. 6, 1993, p. 510-513.

Research output: Contribution to journalArticle

McMichael, J, Lieberman, R, Doyle, H, McCauley, J, Van Thiel, D, Thomson, A, Fung, J & Starzl, TE 1993, 'Computer-guided concentration-controlled trials in autoimmune disorders', Therapeutic Drug Monitoring, vol. 15, no. 6, pp. 510-513.
McMichael J, Lieberman R, Doyle H, McCauley J, Van Thiel D, Thomson A et al. Computer-guided concentration-controlled trials in autoimmune disorders. Therapeutic Drug Monitoring. 1993;15(6):510-513.
McMichael, John ; Lieberman, R. ; Doyle, Howard ; McCauley, J. ; Van Thiel, D. ; Thomson, A. ; Fung, J. ; Starzl, T. E. / Computer-guided concentration-controlled trials in autoimmune disorders. In: Therapeutic Drug Monitoring. 1993 ; Vol. 15, No. 6. pp. 510-513.
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