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

TitleQuality assessment for therapeutic drug monitoring in AIDS Clinical Trials Group (ACTG 5146): a multicenter clinical trial.
Publication TypeJournal Article
Year of Publication2010
AuthorsDiFrancesco R, Rosenkranz S, A Mukherjee L, Demeter LM, Jiang H, DiCenzo R, Dykes C, Rinehart A, Albrecht M, Morse GD
JournalTher Drug Monit
Volume32
Issue4
Pagination458-66
Date Published2010 Aug
ISSN1536-3694
KeywordsAcquired Immunodeficiency Syndrome, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Calibration, Drug Monitoring, HIV Protease Inhibitors, HIV-1, Humans, Laboratories, Quality Control, Specimen Handling, Treatment Outcome
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.

DOI10.1097/FTD.0b013e3181e4427a
Alternate JournalTher Drug Monit
PubMed ID20592644
PubMed Central IDPMC2936454
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