title: 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.affiliation: Department of Pharmacy Practice, SUNY at Buffalo, Buffalo, NY, USA. rda@buffalo.edu
authors.forename: Robin
authors.initials: R
authors.lastname: DiFrancesco
authors.forename: Susan
authors.initials: S
authors.lastname: Rosenkranz
authors.forename: A Lisa
authors.initials: AL
authors.lastname: Mukherjee
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Demeter
authors.forename: Hongyu
authors.initials: H
authors.lastname: Jiang
authors.forename: Robert
authors.initials: R
authors.lastname: DiCenzo
authors.forename: Carrie
authors.initials: C
authors.lastname: Dykes
authors.forename: Alex
authors.initials: A
authors.lastname: Rinehart
authors.forename: Mary
authors.initials: M
authors.lastname: Albrecht
authors.forename: Gene D
authors.initials: GD
authors.lastname: Morse
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D019380:Anti-HIV Agents / Q000097:blood / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D002138:Calibration; D016903:Drug Monitoring / Q000592:standards*; D017320:HIV Protease Inhibitors / Q000097:blood / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D007753:Laboratories / Q000592:standards; D011786:Quality Control; D013048:Specimen Handling / Q000592:standards; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors