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. 2014 Dec 30:238:105-11.
doi: 10.1016/j.jneumeth.2014.09.019. Epub 2014 Sep 26.

A novel open-source drug-delivery system that allows for first-of-kind simulation of nonadherence to pharmacological interventions in animal disease models

Kyle E Thomson  1 , H Steve White  2
Affiliations

A novel open-source drug-delivery system that allows for first-of-kind simulation of nonadherence to pharmacological interventions in animal disease models

Kyle E Thomson et al. J Neurosci Methods. .

Abstract

Background: Nonadherence to a physician-prescribed therapeutic intervention is a costly, dangerous, and sometimes fatal concern in healthcare. To date, the study of nonadherence has been constrained to clinical studies. The novel approach described herein allows for the preclinical study of nonadherence in etiologically relevant disease animal model systems.

New method: The method herein describes a novel computer-automated pellet delivery system which allows for the study of nonadherence in animals. This system described herein allows for tight experimenter control of treatment using a drug-in-food protocol. Food-restricted animals receive either medicated or unmedicated pellets, designed to mimic either "taking" or "missing" a drug.

Results: The system described permits the distribution of medicated or unmedicated food pellets on an experimenter-defined feeding schedule. The flexibility of this system permits the delivery of drug according to the known pharmacokinetics of investigational drugs.

Comparison with other methods: Current clinical adherence research relies on medication-event monitoring system (MEMS) tracking caps, which allows clinicians to directly monitor patient adherence. However, correlating the effects of nonadherence to efficacy still relies on the accuracy of patient journals.

Conclusion: This system allows for the design of studies to address the impact of nonadherence in an etiologically relevant animal model. Given methodological and ethical concerns of designing clinical studies of nonadherence, animal studies are critical to better understand medication adherence. While the system described was designed to measure the impact of nonadherence on seizure control, it is clear that the utility of this system extends beyond epilepsy to include other disease states.

Keywords: Anti-seizure drug; Chronic drug delivery; Drug discovery; Epilepsy; Nonadherence; Noncompliance.

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Figures

Figure 1
Figure 1
Overall System Design. (a) A single modified feeder. (b) System schematic. (c) Populated PCBs that make up the Feeder Control System. (d) Schematic and photo of single, dual feeder cage block.
Figure 2
Figure 2
Feeder control form. This screenshot shows the system control form containing all the information needed to control daily feedings. (a) Feedings, up to 6 per day, are controlled by defining the time (military time), at which the feedings should be executed. A time of 0:00:00 disables that meal. (b) The investigator defines the ratio of pellets to body weight (in grams) per meal. (c) This box enables/disables scheduled feedings. (d) Animal ID#. This is recorded in the software, which allows for unique identification of the animals. Locations match the setup of the room, as illustrated in figure 2c. (e) Animal weight, used to calculate how many pellets are given per meal, in conjunction with (b). (f) Medication %, which determines what percentage of all meals are medicated per week.
Figure 3
Figure 3
Layout of the data flow for feeding control. This setup allows for 24 feeders to be independently controlled with 6 breakout boards, and one main board.
Figure 4
Figure 4
Schematic of the main system control board.
Figure 5
Figure 5
Schematic of the breakout board.
Figure 6
Figure 6
Schematic and logic setup for infrared pellet detection system for the breakout boards and main board. (a) Schematic diagram showing the layout of four feeders’ infrared sensors attached to a single breakout board. While no sensor is blocked, the signal is pulled low. When a pellet crosses in front of the LED, the pull-up resistor drives the signal high. This layout creates a NAND gate. (b) The NAND structures from each of 6 breakout boards are fed into a BJT OR gate on the main board.
See this image and copyright information in PMC

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