Title | Quality assessment for therapeutic drug monitoring in AIDS Clinical Trials Group (ACTG 5146): a multicenter clinical trial. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | DiFrancesco R, Rosenkranz S, A Mukherjee L, Demeter LM, Jiang H, DiCenzo R, Dykes C, Rinehart A, Albrecht M, Morse GD |
Journal | Ther Drug Monit |
Volume | 32 |
Issue | 4 |
Pagination | 458-66 |
Date Published | 2010 Aug |
ISSN | 1536-3694 |
Keywords | Acquired 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. |
DOI | 10.1097/FTD.0b013e3181e4427a |
Alternate Journal | Ther Drug Monit |
PubMed ID | 20592644 |
PubMed Central ID | PMC2936454 |
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