title: Role for direct electronic verification of pharmaceutical ingestion in pharmaceutical development.
abstract: Identifying a dosing regimen for recommended use is one of the more difficult tasks in pharmaceutical development and has major therapeutic and economic consequences. In the clinical phase of pharmaceutical development, pharmacokinetic-pharmacodynamic (PK/PD) models are used to characterize the relationship between drug exposure and clinical outcome. When adherence to the prescribed drug dosage is known, true dose-response can be validly estimated, while non-compliance with the nominal prescribed dosage causes unintended variability in actual drug exposure and ensuing difficulty in determining dose-response. The purpose of this manuscript is to provide an overview of the important role that adherence plays in the interpretation of clinical studies for pharmaceutical development, to summarize the challenges in utilizing currently available tools for assessing adherence, to characterize the attributes of an ideal adherence marker, and to describe the utilization of a networked system having an ingestible sensor for direct confirmation of pharmaceutical utilization in drug development studies. The positive detection accuracy of this networked system when compared to direct ingestion is 99.3% [95%CI: 0.977, 0.999]. A direct measure of pharmaceutical utilization in pharmaceutical studies provides the means to examine the temporal patterns of drug response that are engendered by patients' actual dosing patterns, and to characterize more accurately exposure-response relationships. Materials and methods are available to accomplish these goals.
authors.affiliation: Proteus Biomedical, Incorporated, Redwood City, CA, USA. ldicarlo@proteusbiomed.com
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: DiCarlo
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D003625:Data Collection / Q000295:instrumentation / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D055118:Medication Adherence; D008991:Monitoring, Physiologic / Q000295:instrumentation / Q000379:methods; D012107:Research Design