Limits of Confidence in Tracer Compounds as a Means of Measuring Patient Compliance with Medication

Abstract

Chemical tracers are thought to be a desirable means of measuring patient compliance with medication. However, no compound has emerged as a standard. To explain this observation, the authors explored the mathematics of simulated tracers with half-lives 5 to 140 days over a month of daily dosing. To model assay variability, they added random "noise" to calculated tracer serum levels. They then fitted those altered levels to the dosing pattern most likely to have produced them, given known kinetics of the tracers. The large number of possible dosing patterns over a month (268,435,456) magnified uncertainty in interpreting noise-altered levels. At best, with an assay variability of 5%, compliance could be estimated only within 4 to 8 doses per month. The tracer with a half-life of 30 days performed best. Pairing tracers did not improve uncertainty. The authors found that even a model neglecting many real-world variables suggests a limited role for tracers in measuring compliance.

Measurement of psychiatric treatment adherence

“…Because of the problems with mapping medication levels to adherence, some adherence studies have used biologic tracers added to the medication [35]. These tracers are selected based on their safety, detectability in biological samples, consistency of levels within and across patients for a given medication dose, and for being essentially inert with respect to therapeutic effects or interactions with other drugs.…”

“…Producing a tracer that possesses all of these attributes is difficult and expensive, resulting in this method seldom being used. Mathematical modeling of simulated tracers with varying half-lives suggests that tracers may be accurate only within 4 to 8 doses per month under the best of conditions [35]. Further research is needed on developing inexpensive tracers that are sensitive to small changes in adherence.…”

Population‐based pharmacokinetic approach for methadone monitoring of opiate addicts: potential clinical utility

“…Methadone dose correlates well with plasma concentration (Loimer & Schmid, 1994), but only about 80% of the observed variability in methadone concentration can be attributed to dose consumed (Wolff et al, 1991b). The use of individual kinetic parameters in combination with plasma drug measurements gives valuable information that can be related to the likelihood of following a prescribed dosage regimen (Shine & McDonald, 1999). Hence individual kinetic parameters will be useful in helping to discern unaccounted for variability in methadone metabolism.…”