Quality assessment for therapeutic drug monitoring in AIDS Clinical Trials Group (ACTG 5146): a multicenter clinical trial.

Abstract

In a randomized trial, AIDS Clinical Trials Group (ACTG) protocol 5146 (A5146) investigated the use of therapeutic drug monitoring (TDM) to adjust doses of HIV-1 protease inhibitors (PIs) in patients with prior virologic failure on PI-based therapy who were starting a new PI-based regimen. The overall percentage of "PI trough repeats" such as rescheduled visits or redrawn PI trough specimens increased from 2% to 5% to 10% as the process progressed from the clinical sites, the pharmacology specialty laboratory, and the study team, respectively. Cumulatively, this represents a 17% rate of failure to obtain adequate PI trough sample. While targeting a turnaround of 7 days or less from sample receipt to a drug concentration report, 12% of the received specimens required a longer period to report concentrations. The implementation of dosing changes in the TDM arm were achieved within 7 days or less for 56% of the dose change events and within 14 days or less for 77% of dose change events. This quality assurance analysis provides a valuable summary of the specific points in the TDM process that could be improved during a multicenter clinical trial including: 1) shortening the timeline of sample shipment from clinical site to the laboratory; 2) performing the collection of PI trough specimen within the targeted sampling window by careful monitoring of the last dose times and collection times by the clinicians; 3) increasing patient adherence counseling to reduce the number of samples that are redrawn due to suspecting inconsistent adherence; and 4) decreasing the time to successful TDM-based dose adjustment. The application of some of these findings may also be relevant to single-center studies or clinical TDM programs within a hospital.

• Authors: Robin DiFrancesco, Susan Rosenkranz, A Lisa Mukherjee, Lisa M Demeter, Hongyu Jiang, Robert DiCenzo, Carrie Dykes, Alex Rinehart, Mary Albrecht, Gene D Morse
• Journal: Therapeutic drug monitoring (Ther Drug Monit) Vol. 32 Issue 4 Pg. 458-66 (Aug 2010) ISSN: 1536-3694 [Electronic] United States
• PMID: 20592644 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• HIV Protease Inhibitors

Topics

• Acquired Immunodeficiency Syndrome (drug therapy)
• Anti-HIV Agents (blood, therapeutic use)
• Antiretroviral Therapy, Highly Active (methods)
• Calibration
• Drug Monitoring (standards)
• HIV Protease Inhibitors (blood, therapeutic use)
• HIV-1
• Humans
• Laboratories (standards)
• Quality Control
• Specimen Handling (standards)
• Treatment Outcome