Quality Assessment for Therapeutic Drug Monitoring in AIDS Clinical Trials Group (ACTG 5146): A Multicenter Clinical Trial

摘要

In a randomized trial, AIDS Clinical Trials Group (ACTG) protocol 5146 (A5146) investigated the use of 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 PSL, and the study team, respectively. Cumulatively, this represents a 17% rate of failure to obtain adequate PI trough sample. While targeting a turn-around of ≤ 7 days 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 for 56% of the dose change events, and within ≤14 days 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 lab, [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.