U.S. patent application number 16/435018 was filed with the patent office on 2019-10-10 for system for ingestion event monitoring and method for detecting ingestion events with high accuracy.
This patent application is currently assigned to etectRx, Inc.. The applicant listed for this patent is etectRx, Inc.. Invention is credited to Neil R. EULIANO, Glen Flores, Brent Myers.
Application Number | 20190307363 16/435018 |
Document ID | / |
Family ID | 61902406 |
Filed Date | 2019-10-10 |
![](/patent/app/20190307363/US20190307363A1-20191010-D00000.png)
![](/patent/app/20190307363/US20190307363A1-20191010-D00001.png)
![](/patent/app/20190307363/US20190307363A1-20191010-D00002.png)
![](/patent/app/20190307363/US20190307363A1-20191010-D00003.png)
![](/patent/app/20190307363/US20190307363A1-20191010-D00004.png)
United States Patent
Application |
20190307363 |
Kind Code |
A1 |
EULIANO; Neil R. ; et
al. |
October 10, 2019 |
SYSTEM FOR INGESTION EVENT MONITORING AND METHOD FOR DETECTING
INGESTION EVENTS WITH HIGH ACCURACY
Abstract
System and method for ingestion event detection and monitoring
are disclosed. The system comprises: an ingestible microsensor
configured to generate a signal representing an ingestion event
upon ingestion and contact with stomach fluid of a patient; and a
reader device positioned external to the patient and configured to
detect the signal representing the ingestion event with at least
95% accuracy.
Inventors: |
EULIANO; Neil R.;
(Gainesville, FL) ; Myers; Brent; (Palm Bay,
FL) ; Flores; Glen; (Gainesville, FL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
etectRx, Inc. |
Gainesville |
FL |
US |
|
|
Assignee: |
etectRx, Inc.
Gainesville
FL
|
Family ID: |
61902406 |
Appl. No.: |
16/435018 |
Filed: |
June 7, 2019 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
15783801 |
Oct 13, 2017 |
10321849 |
|
|
16435018 |
|
|
|
|
62407913 |
Oct 13, 2016 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/073 20130101;
A61B 2562/162 20130101; A61B 2560/0214 20130101; A61B 5/4833
20130101 |
International
Class: |
A61B 5/07 20060101
A61B005/07; A61B 5/00 20060101 A61B005/00 |
Goverment Interests
STATEMENT OF FEDERALLY FUNDED RESEARCH
[0002] This invention was made with government support under
contract 4R44DA036277-02 awarded by the National Institute on Drug
Abuse (NIDA) of the National Institutes of Health. The government
has certain rights in the invention.
Claims
1-2. (canceled)
3. A system for ingestion event monitoring, the system comprising:
an ingestible microsensor configured to generate a signal
indicating an ingestion event upon ingestion and contact with
stomach fluid of a patient; and a reader device positioned external
to the patient and configured to detect the signal indicating the
ingestion event with at least 95% accuracy.
4. The system of claim 3, further comprising a remote database
configured to receive data from the reader device via a
communication network in real time, and generate and transmit one
or more messages at least to the patient based upon received data
from the reader device.
5. The system of claim 3, wherein the ingestible microsensor
comprises circuitry configured to generate power upon being exposed
to the stomach fluid of the patient.
6. The system of claim 5, wherein the ingestible microsensor is
configured to generate and transmit the signal using the power over
a period of time following ingestion.
7. The system of claim 3, wherein the ingestible microsensor is
configured to be associated with a unique identifier, and the
signal comprises data indicating the unique identifier.
8. The system of claim 3, wherein the reader device requires no
skin contact with the patient.
9. The system of claim 3, wherein the signal is a radio frequency
signal.
10. The system of claim 6, wherein the period of time is
approximately 30 minutes.
11. The system of claim 3, wherein the reader device is configured
to upload data stored thereon to a software system via at least one
of a cellular communication protocol, a bluetooth communication
protocol, and a universal serial bus.
12. The system of claim 4, wherein the data received by the remote
database from the reader device are encrypted.
13. The system of claim 4, wherein the data from the reader device
comprise data indicating a unique identifier associated with the
reader device, an antenna connection status, an on-charger status,
a reader device battery status, and reader device status
messages.
14. A method for ingestion event monitoring, the method comprising:
embedding an ingestible microsensor in an oral dosage form to be
consumed by a subject; and having the subject ingest the oral
dosage form; wherein the ingestible microsensor is configured to
generate a signal indicating an ingestion event upon contact with
stomach fluid of the subject, and transmit the signal to a reader
device positioned external to the subject, wherein the reader
device is configured to detect the signal with at least 95%
accuracy.
15. The method of claim 14, further comprising: configuring a
remote database to receive data from the reader device via a
communication network in real time; and generating and
transmitting, by the remote database, one or more messages at least
to the patient based upon received data from the reader device.
16. The method of claim 14, further comprising: generating, by
circuitry of the ingestible microsensor, power after the ingestible
microsensor is exposed to the stomach fluid of the patient; and
generating and transmitting, by the ingestible microsensor, the
signal using the power over a period of time following ingestion,
wherein the period of time is approximately 30 minutes.
17. The method of claim 14, further comprising associating a unique
identifier with the ingestible microsensor, wherein the signal
comprises data indicating the unique identifier.
18. The method of claim 14, wherein the reader device requires no
skin contact with the patient.
19. The method of claim 14, wherein the signal is a radio frequency
signal.
20. The method of claim 14, further comprising uploading data
stored on the reader device to a software system via at least one
of a cellular communication protocol, a bluetooth communication
protocol, and a universal serial bus.
21. The method of claim 14, wherein the data received by the remote
database from the reader device are encrypted.
22. The method of claim 15, wherein the data from the reader device
comprise data indicating a unique identifier associated with the
reader device, an antenna connection status, an on-charger status,
a reader device battery status, and reader device status messages.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional
Patent Application No. 62/407,913, filed Oct. 13, 2016.
TECHNICAL FIELD OF THE INVENTION
[0003] The present invention relates in general to the fields of
ingestion event monitoring, patient compliance with pharmaceutical
prescriptions and clinical trial protocols, and reporting of
medication adherence data.
SUMMARY OF THE INVENTION
[0004] The present invention is directed to a system for monitoring
ingestion events and methods of detecting ingestion events with
high accuracy. The system is a novel technology that provides an
objective measure of medication ingestion and enables real-time
reporting of verified medication adherence data. The system
includes an ingestible microsensor that is embedded in an oral
dosage form and, once activated by stomach fluid, communicates
digital messages to an external wearable reader to confirm
ingestion. The detection rate of the system for detecting ingestion
events is preferably at least 95%, more preferably at least 97%,
further preferably 99% and most preferably 100%.
BRIEF DESCRIPTION OF THE DRAWINGS
[0005] The accompanying drawings, which are incorporated into and
constitute a part of this specification, illustrate one or more
example aspects of the present disclosure and, together with the
detailed description, serve to explain their principles and
implementations.
[0006] FIG. 1 illustrates an ID-Cap system comprising an
ID-Capsule, an ID-Cap Reader, and a remote Data Management System,
according to an exemplary aspect;
[0007] FIG. 2 illustrates the ID-Capsule of the ID-Cap system of
FIG. 1, according to an exemplary aspect;
[0008] FIG. 3 illustrates the ID-Cap Reader of the ID-Cap system of
FIG. 1, according to an exemplary aspect; and
[0009] FIG. 4 is a diagram showing system operations among various
components of the ID-Cap system of FIG. 1, according to an
exemplary aspect.
DETAILED DESCRIPTION OF THE INVENTION
[0010] The present invention is directed to a system for monitoring
ingestion events and methods of detecting ingestion events with
high accuracy. The system is a novel technology that provides an
objective measure of medication ingestion and enables real-time
reporting of verified medication adherence data. The system
includes an ingestible microsensor that is embedded in an oral
dosage form and, once activated by stomach fluid, communicates
digital messages to an external wearable reader to confirm
ingestion. The accuracy of the system for detecting ingestion
events is preferably at least 95%, more preferably at least 97%,
further preferably 99% and most preferably 100%.
[0011] The inventive system is also referred to herein as "the
ID-Cap System."
[0012] Nonadherence to prescribed medications is an important
consideration in the clinical management of patients and in
clinical research and drug development. Considerable research has
been conducted to elucidate the reasons for nonadherence, which are
often unique to the individual patient and the specific medication
of interest. [1] Across different disease states and medications,
nonadherence directly impacts drug exposure and therapeutic
outcomes. An estimated 50% of patients in developed countries are
not adherent to prescribed medications for chronic health
conditions, and the magnitude and impact of the problem are even
greater in developing countries. [2] Poor adherence is associated
with increased healthcare costs and contributes over $100 billion
in avoidable medical costs in just the United States alone. [3] The
accurate detection and reporting of medication nonadherence are
critical for healthcare providers, payers, and clinical researchers
to evaluate and optimize therapeutic interventions. Current methods
that are commonly used for monitoring medication adherence, such as
patient self-reports, pill counts, and prescription refill
histories, comprise indirect measures that are generally incomplete
and inaccurate and cannot be effectively utilized for understanding
and tracking actual medication use. [4] Reliable methods for
objectively measuring medication adherence behaviors that can be
easily implemented for remote health monitoring are needed.
[0013] The ID-Cap System is a novel technology that provides an
objective measure of medication ingestion and enables real-time
reporting of verified medication adherence data at the dose level.
The system is classified as an ingestible event monitoring system
and used for detecting the presence of an ingested solid oral
dosage form inside the gastrointestinal (GI) tract. Ingestible
medical devices have been well-characterized in the scientific
literature and regulatory approval processes. The ID-Cap System
consists of an ingestible microsensor that is embedded in an oral
dosage form and, once activated by stomach fluid, communicates
digital messages to an external wearable reader to confirm
ingestion. The adherence data, including time-stamped messages
verifying ingestion, are transmitted to a secure, centralized
database via the mobile phone network. The collection and real-time
reporting of accurate medication adherence data has the potential
to strengthen health information datasets and significantly improve
medication use and therapeutic outcomes.
[0014] A study was conducted to evaluate the accuracy of the system
for detecting ingestion events. The study design included the
following three phases: 1) screening phase, 2) treatment phase
consisting of 20 daily capsule ingestion events over a four-week
period, and 3) follow-up phase consisting of a follow-up study
visit that included an abdominal X-ray and a follow-up phone call.
The initial use of the ID-Cap reader and ingestion of the first
study capsule were directly observed by an investigator during the
first study visit. Subsequent study capsule ingestions were
completed outside the research facility at the study participant's
home or other location of their choice with ingestion assessed
using the ID-Cap System.
[0015] Twenty (20) healthy volunteers were enrolled in this
four-week pilot study. Study measurements included ID-Tag detection
indicating capsule ingestion, utilization of the ID-Cap System
consistent with instructions for use, adverse event reports,
discontinuations of the System during the study, and safety
assessments related to excretion of the ID-Tags through abdominal
X-ray evaluations.
[0016] Positive detection accuracy was 100% for the 20
directly-observed ingestions of study capsules that occurred during
the initial study visits. Of the 384 ingestion events that were
self-administered by the study participants without direct
observation, 371 were accurately detected using the ID-Cap System.
Overall adherence to the prescribed study capsules as measured by
the ID-Cap System was 97.75% (391 detections/400 expected ingestion
events). Significant intra-individual and inter-individual
variability in the timing of self-administered doses was observed
in this study. No adverse events were reported, and no study
participants discontinued use of the ID-Cap System for any reason
during the study. There was no evidence indicating retention of
ID-Tags based on abdominal X-ray evaluations.
[0017] The ID-Cap System enables accurate measurement of medication
adherence for oral drug therapy at the dose level. This study
supports the clinical validation of the technology and feasibility
in using the system for the collection and real-time reporting of
medication adherence in the clinical management of patients and in
clinical research and drug development.
[0018] The objective of this exploratory study was to evaluate the
performance, reliability, usability, and safety of the ID-Cap
System for remote monitoring of 20 ingestion events over four weeks
in 20 healthy volunteers.
Methods
Study Participants
[0019] Twenty (20) healthy volunteers were screened and enrolled in
this four-week pilot study. Individuals aged 18 to 45 years who
were deemed healthy by the study physician as determined by past
medical and surgical history, physical examination, and vital signs
at screening were eligible for enrollment in the study. To be
eligible, individuals had to weigh at least 50 kg and have a body
mass index (BMI) within the range of 18 to 35. Exclusion criteria
for the study included the following: [0020] Any known
hypersensitivity to silver or magnesium [0021] Difficulty
swallowing solids and/or capsules [0022] Any implanted electronic
device [0023] A significant illness within two weeks of entering
the study [0024] A history of drug or alcohol abuse within the six
months prior to screening [0025] Participation in another study at
the time of screening or those who have taken an investigational
drug within 30 days of enrollment [0026] A significant medical
and/or mental condition that would compromise the study
participant's welfare or confound the results of this study in the
opinion of the investigator [0027] Pregnancy
Materials
[0028] The ID-Cap System may comprise an ingestible sensor system
for use in the real-time monitoring and reliable reporting of
patient adherence to medication protocols. The ID-Cap System
provides an in vivo communications platform that enables
verification of oral medication ingestion through detection of the
presence of an ingested solid oral dosage form inside the GI tract.
Referring to FIG. 1, the ID-Cap System 100 is comprised of three
key components: 1) The ID-Tag 102, an ingestible component that
sends information from within the body after it has been ingested.
2) The ID-Cap Reader 104, an external receiver that records the
data transmitted by the ID-Tag. and 3) An information system 106
configured to monitor ingestion events, manage the data, and send
messages to study participants.
[0029] As shown in FIG. 2, the ID-Tag 102 is a small, biocompatible
ingestible device that is composed of an integrated circuit on a
flexible film (23 mm.times.10.5 mm.times.300 microns). The ID-Tag
102 has an exposed sensor that is intended to safely come into
contact with the gastrointestinal fluids. The exposed metal
elements of the sensor (i.e., magnesium and silver chloride) serve
as a battery which powers the ID-Tag 102 to generate the in-body
communication signal. Within a few minutes after ingestion of the
ID-Tag 102, an electrolyte in the stomach. chloride, powers up the
tiny battery on the surface of the ID-Tag 102. This process is
independent of the pH of the stomach. The ID-Tag 102 generates a
radio frequency signal that propagates through the body and can be
detected by the ID-Cap Reader 104, an external receiver. Once
ingested and activated, the ID-Tag 102 will transmit the in-body
communication signal for approximately 30 minutes on average. After
sending the digital messages to the reader 104, the ID-Tag 102
becomes inactive and is excreted intact in the feces. Each ID-Tag
102 can be assigned a distinct identifier, enabling multiple
ID-Tags to be detected and differentiated when they are ingested at
or around the same time. All materials in the ID-Tag 102 are
biocompatible and are either known to be safe or have been safely
utilized in other approved ingestible medical devices.
[0030] The ID-Tag 102 can be easily incorporated into a capsule for
the purpose of providing adherence data for the medication dose
that is delivered in the capsule. In this study, the ID-Tag 102 was
encapsulated within a size 00 clear hard gelatin capsule that also
contained a size 1 hard gelatin capsule filled with sucrose. While
the capsules administered in this study represented placebo
capsules, the size 00 capsule shell containing the ID-Tag 102
provides a well-characterized and convenient vehicle for delivery
of active pharmaceutical ingredients, oral dosage forms, or other
ingestible products for which ingestion events will be
monitored.
[0031] Referring to FIGS. 3 and 4, the ID-Cap Reader 104 is a
wearable, battery-powered, digital radio transceiver that detects
the signal generated by the ID-Tag 102 following its ingestion. For
this study, the ID-Cap Reader 104 (10 cm.times.6 cm.times.2.5 cm)
was clipped onto a belt or waistband, and the accompanying patch
antenna (16 cm.times.5.7 cm) was affixed to the skin of the abdomen
and connected to the reader with a thin coaxial cable. Study
participants were instructed to apply the patch and connect the
reader before taking their study capsule and to leave it on for one
hour following capsule ingestion. Study participants were also
instructed to keep the ID-Cap Reader 104 plugged into an AC power
outlet to charge it when they were not wearing the device. A unique
ID-Cap Reader 104 was assigned to each study participant.
[0032] The wearable reader has three options for uploading data to
the software system: cellular. Bluetooth. and USB. The cellular and
Bluetooth capabilities allow real-time communication of ingestion
events to enable real-time monitoring of medication adherence
events and automated, context-sensitive messaging. The stored,
encrypted data are securely and privately transmitted from the
ID-Cap Reader 104 to the central database. The data transmitted by
the ID-Cap Reader 104 include the ID-Tag information, unique
identifier for the ID-Cap Reader 104, antenna connection status,
on-charger status, reader battery status, and device status
messages. No personally identifiable information is stored on the
ID-Cap Reader 104 or otherwise transmitted throughout the process.
The data remain stored on the ID-Cap Reader 104 and can be
downloaded directly from the reader as necessary.
Study Design
[0033] This open-label, single-arm exploratory study evaluated the
performance, reliability, usability, and safety of the ID-Cap
System 100 for remote monitoring of 20 ingestion events over four
weeks in 20 healthy volunteers. The study endpoints included ID-Tag
detection indicating capsule ingestion, utilization of the ID-Cap
System 100 consistent with instructions for use, adverse event
reports, discontinuations of the System during the study, and
safety assessments related to excretion of the ID-Tags through
abdominal X-ray evaluations. The study was reviewed and approved by
the Western Institutional Review Board (WIRB, Puyallup. Wash.).
[0034] The study design included the following three phases: 1)
Screening Phase, 2) Treatment Phase consisting of 20 daily capsule
ingestion events over a four-week period, and 3) Follow-Up Phase
consisting of a follow-up study visit that included an abdominal
X-ray and a follow-up phone call.
Screening Phase
[0035] Healthy volunteers were screened to determine eligibility
for enrollment in the study. Past medical and surgical history,
medication history for the prior 30 days, physical examination,
body height, body mass index, and vital signs were recorded during
the screening visit. After receiving information about the study,
each eligible study participant signed the informed consent form.
Female participants were given a urine pregnancy test before the
treatment phase, at the mid-point of the treatment phase, and
before the abdominal X-ray conducted at the follow-up visit. All
current medications, as well as their doses and routes of
administration, were recorded at the screening visit and at each
subsequent study visit.
[0036] All study participants were enrolled in a mobile phone
message system used to send reminder messages to their personal
mobile phones. At a predetermined time each day, the participant
received a text message reminding him or her to put on the ID-Cap
Reader 104 as directed and to ingest the study capsule if the
appropriate ingestion event had not already been recorded.
Participants were instructed to call the study staff if any unusual
or adverse events were noted between study visits. The study
participant also received a follow-up text message one hour after
the initial text message if an anticipated ingestion event was not
detected with the ID-Cap System 100 within that time window.
Treatment Phase
[0037] During the first study visit, participants were reminded of
the study plan, provided instructions for taking study capsules,
and trained to use the ID-Cap System 100. Study participants were
instructed to take one study capsule every day with sufficient
water or fluid to comfortably swallow the capsule. They received
direction to put on the fully-charged ID-Cap Reader 104 before
taking the study capsule and wear it continuously for one hour
following capsule ingestion. They were instructed to clip the
reader onto a belt or waistband and affix the patch antenna to the
skin of the abdomen. They were instructed to replace the patch
antenna after each use and to dispose of the used patch antenna.
Study participants received instructions on how to charge the
reader when not in use. The study capsule consisted of a size 00
hard gelatin capsule that encapsulated both an ID-Tag and a smaller
size 1 hard gelatin capsule filled with sucrose.
[0038] At the first study visit, the initial use of the ID-Cap
Reader 104 and ingestion of the first study capsule were directly
observed by the investigator. The investigator recorded the date
and time of capsule ingestion, monitored the participant for one
hour following ingestion, and reported any adverse events.
Subsequent ingestions (i.e., study capsules 2 through 20) were
completed outside the research facility at the study participant's
home or other location of their choice with ingestion assessed
using the ID-Cap System 100. The participant was instructed to
record in writing the capsule identification code and the date and
time when they took each study capsule on a log that was attached
to the back of the ID-Cap Reader 104. The reader 104 was returned
to the research facility each week to download the data that were
securely stored on it. Study capsules were dispensed to the
participant each week. Each study participant received five study
capsules to take over the course of a week for four consecutive
weeks. Weekly study visits were scheduled with each participant for
return of the reader, dispensing of capsules, and collection of any
adverse events or usability issues.
[0039] Study participants were instructed to call the investigator
if they experienced any unusual or adverse events during the
treatment phase. If study personnel observed that an assigned
device was not functioning as intended or if they were notified of
the same, the device was repaired or replaced as needed. If the
study participant did not properly recharge the reader prior to its
use before taking a study capsule, a replacement capsule was
provided for inclusion in the evaluation and the study participant
was reminded to use the system as instructed. The data collected
from the ID-Cap System 100 included presence of the signal from the
ingested ID-Tag 102, other electrical information such as the
strength and frequency of the received signal, and information
about the status of the reader 104.
Follow-Up Phase
[0040] A follow-up study visit conducted at a radiology facility
was scheduled within 10 to 14 days after the last study capsule
ingestion for assessment of the safety and tolerability of the
ID-Cap System 100. This follow-up visit was scheduled with each
study participant who ingested at least one study capsule. During
the follow-up visit, each study participant met with the
investigator for the documentation of any adverse events and
received an abdominal X-ray to assess retention of ID-Tags. Female
participants were given a urine pregnancy test before the X-ray.
Each study participant received a follow-up phone call from the
investigator within 30 days after the last study capsule ingestion
to assess for any adverse events and to document any changes noted
during the study. Changes to medications were also recorded at the
follow-up visit and follow-up phone call.
Statistical Analysis Plan
[0041] All statistical analyses were descriptive. Summary data for
the performance, reliability, and usability of the ID-Cap System
100 included all study participants who ingested at least one study
capsule. Summary data for safety and tolerability included all
study participants who ingested at least one study capsule.
Results
[0042] Twenty-eight (28) individuals were screened to determine
eligibility for participation, and 20 healthy volunteers were
enrolled in the study. The study population included 12 males and 8
females with a range of ages from 20 to 46 years. Study
participants included 15 Caucasian. 3 Hispanic, and 2
African-American individuals with a mean body mass index of 27.8
(range of 20.0 to 34.5). Table 1 provides the demographic
information for the 20 enrolled participants.
TABLE-US-00001 TABLE 1 Study Demographics and Results Additional
Detection of Study Subject Age Weight Study Capsule Capsule ID
(years) Sex Race Height (pounds) BMI Ingestion Taken* 20-20-001 28
F Caucasian 5' 111 21.7 20/20 (100%) 1 20-20-002 24 F Caucasian
5'5'' 167 27.8 20/20 (100%) 20-20-003 35 F Caucasian 4'11'' 128
25.9 20/20 (100%) 20-20-004 23 M Caucasian 6'0.5'' 147 19.7 18/20
(90%) 20-20-005 28 M Caucasian 6'4'' 235 28.6 19/20 (95%) 20-20-006
29 M Caucasian 6'2'' 214 27.5 19/20 (95%) 20-20-007 41 M Caucasian
5'9'' 206 30.4 20/20 (100%) 1 20-20-008 27 M Hispanic 5'6'' 176
28.4 20/20 (100%) 20-20-009 20 M Hispanic 6' 225 30.5 19/20 (95%) 1
20-20-010 26 F Hispanic 5'6'' 140 22.6 19/20 (95%) 20-20-011 30 F
Caucasian 5'3'' 189 33.5 20/20 (100%) 20-20-012 36 M African
American 6'6'' 231 26.7 19/20 (95%) 20-20-013 25 M Caucasian 6'1''
211 27.8 20/20 (100%) 20-20-014 25 M African American 5'6'' 178
28.7 20/20 (100%) 20-20-015 28 F Caucasian 5'5.75'' 212 34.5 20/20
(100%) 1 20-20-018 21 M Caucasian 5'11.75'' 239.5 32.7 20/20 (100%)
20-20-025 30 F Caucasian 5''8.25'' 154 23.2 20/20 (100%) 20-20-026
31 M Caucasian 6'0.5'' 190 25.8 20/20 (100%) 20-20-027 46 F
Caucasian 5'5'' 154 25.6 19/20 (95%) 20-20-028 34 M Caucasian
5'10'' 240 34.4h 20/20 (100%) *Additional study capsule taken due
to operator error in fully charging the ID-Cap Reader before use of
the ID-Cap System.
[0043] Each study participant used the ID-Cap System 100 and took
20 study capsules once daily as directed over a four-week period.
No study participants prematurely discontinued use of the ID-Cap
System 100 or stopped taking study capsules prior to the end of the
treatment period. Performance, Reliability. and Usability for
Ingestion Event Monitoring
[0044] A total of 20 study capsules were dispensed to each study
participant during the study with instructions to take one capsule
once daily. Four study participants were asked to take one
additional study capsule as a replacement for an ingestion event
that was not recorded due to operator error. In these situations,
the study participant did not follow the instructions for
recharging the reader prior to its use. A total of 404 study
capsules were dispensed to study participants throughout the study,
and, thus, 404 ingestion events were remotely monitored using the
ID-Cap System 100.
[0045] Positive detection accuracy was 100% for the 20
directly-observed ingestions of study capsules that occurred during
the initial study visits for all participants. Of the 384 ingestion
events that were self-administered by the study participants
without direct observation, 371 were accurately detected using the
ID-Cap System 100. Overall adherence to the prescribed study
capsules as measured by the ID-Cap System 100 was 97.75% (391
detections/400 expected ingestion events) when the reader was used
by the study participants according to the instructions for use
(excluding the four ingestion events that were not recorded due to
operator error for which replacement capsules were tracked). Nine
(2.25%) ingestion events were not detected by the system within the
one-hour detection window of reader use following self-reported
ingestion.
[0046] The ID-Cap Readers 104 collected and reliably stored data
for all 391 events that were detected using the ID-Cap System 100.
Data for 385 of the 391 (98.47%) recorded ingestion events were
remotely transmitted from the reader to the secure server in real
time. Data for the remaining six ingestion events were downloaded
to the server when the reader was returned to the research facility
by the study participant. Text notifications of
successfully-reported ingestion events were automatically sent to
each study participant within two to four minutes of the reader
detecting a positive signal.
[0047] The time that each ingestible sensor was detected in the
gastrointestinal tract, indicating when the ID-Tag 102 generated a
signal, was also reported using the ID-Cap System 100. Significant
intra-individual and inter-individual variability in the timing of
self-administered doses was observed in this study.
Safety and Tolerability
[0048] No adverse events were reported throughout the study, either
through self-reporting by study participants or assessments by
study personnel at pre-specified data collection points. No study
participants discontinued use of the ID-Cap System 100 for any
reason during the study. There was no evidence indicating retention
of ID-Tags 102 in any of the 20 study participants based on
abdominal X-ray evaluations conducted during follow-up study
visits.
[0049] This study of the ID-Cap System 100, a novel ingestible
sensor system to directly measure medication adherence, provides
new information on the performance and potential use of this
technology in patient management and clinical trials. The system
demonstrated 97.75% accuracy in detecting oral medication use at
the level of each dose. In this study, the high level of adherence
to self-administered therapy may have been influenced by the daily
reminder text messages, weekly study visits allowing reinforcement
of medication taking, and, most likely, the well-documented
Hawthorne effect. [6] With regard to the latter, the ID-Cap System
100 allows verification and active oversight of medication taking,
and study participants were made aware of this functionality and
goal of the system through the informed consent process. While the
study evaluated the technical feasibility of automated text message
reminders as a means for engaging patients related to actual
medication use, the study was not designed to modify patient
behavior, but rather to report on actual behavior related to
medication ingestion. No specific adherence interventions were
planned in this study beyond automated reminder text messages and
reminder calls from the study investigator, and this presents an
area for future study.
[0050] For the nine ingestion events that were not detected by the
system within the one-hour detection window (9 of 400 events, or
2.25%), either the ID-Tag 102 within the study capsule failed to
power up properly or the reader failed to detect the signal
generated by the activated ID-Tag 102. The study participants
utilized the ID-Cap System 100 over four weeks and a total of 20
doses, demonstrating consistent performance throughout the study
and potential applications in monitoring adherence and persistence
for chronic medications. The reliability of the verified adherence
data generated using this innovative system and valuable
information regarding timing of dose ingestion and inter-dose
intervals enable meaningful use of this information to transform
healthcare and efficiently advance clinical trials. This technology
offers unique and valuable insights into actual medication use and
objective evidence of adherence, or lack thereof, to strengthen
patient treatment plans and clinical research protocols.
[0051] This study demonstrated that the ID-Cap System 100 can be
successfully used by study participants after simple instruction.
User error that impacted system performance occurred in only four
instances out of the 404 ingestion events that were monitored
throughout this study. Several factors were identified during this
study that could contribute to potential failures of the system,
including the limited reader battery life, durability of the reader
when dropped or exposed to fluids, and design elements that impact
patient acceptability and use (e.g., an adhesive patch on the
skin). The manufacturer of the ID-Cap System 100 has developed
strategies to mitigate the identified risks and has designed a new
reader to enhance performance and usability. The system was well
tolerated across study participants with no adverse events reported
and no discontinuations of the system throughout the 20 days of
use. Of note, participants kept the adhesive patch antenna on their
abdomen for a limited duration of one hour following capsule
ingestion.
[0052] Published research involving other ingestible sensor systems
have reported significant skin irritation issues with adhesive
patches that are used as components of these systems for longer
durations. [7] In a preferred embodiment, another version of the
ID-Cap System 100 may use external wearable readers that do not
require skin contact or adhesive patches, modules that allow
integration into widely-used wearable and patient monitoring
devices, and other patient-centered form factors, all of which are
enabled by the unique in-body communications platform of the ID-Cap
System 100.
[0053] The ID-Cap System 100 enables accurate measurement of
medication adherence for oral drug therapy at the dose level. This
study supports the clinical validation of the technology and
feasibility in using the system for the collection and real-time
reporting of medication adherence in the clinical management of
patients and in clinical research and drug development.
REFERENCES
[0054] [1] Brown M, Bussell J. Medication adherence: WHO cares?
Mayo Clin Proc 2011; 86(4):304-314. [0055] [2] Sabate E, ed.
Adherence to Long-Term Therapies: Evidence for Action. Geneva,
Switzerland: The World Health Organization; 2013. [0056] [3] IMS
Institute for Healthcare Informatics. Avoidable costs in U.S.
healthcare. 2013. Available at: [0057]
http://www.imshealth.com/deployedfiles/imshealth/Global/Content/Co-
rporate/IMS
%20Institute/RUOM-2013/IHII_Responsible_Use_Medicines_2013.pdf.
Accessed Nov. 5, 2015. [0058] [4] Osterberg L, Blaschke T.
Adherence to medication. N Engl J Med 2005; 353(5):487-497. [0059]
[5] Kiourti A. Psathas K. Nikita K. Implantable and ingestible
medical devices with wireless telemetry functionalities: a review
of current status and challenges. Bioelectromagnetics 2014;
35:1-15. [0060] [6] Davis S, Feldman S. Using Hawthorne effects to
improve adherence in clinical practice: lessons from clinical
trials. JAMA Dermatol 2013; 149(4):490-491. [0061] [7] Eisenberger
U, Wiithrich R. Bock A, et al. Medication adherence assessment:
high accuracy of the new ingestible sensor system in kidney
transplants. Transplantation 2013; 96:245-250.
* * * * *
References