U.S. patent application number 13/953503 was filed with the patent office on 2014-04-17 for clinical monitoring device with time shifting capability.
The applicant listed for this patent is Michael Hufford, Jonathan McClelland, Kevin Dennis O'Keefe, Jean Paty, David Peterson, Saul Shiffman. Invention is credited to Michael Hufford, Jonathan McClelland, Kevin Dennis O'Keefe, Jean Paty, David Peterson, Saul Shiffman.
Application Number | 20140108032 13/953503 |
Document ID | / |
Family ID | 47391494 |
Filed Date | 2014-04-17 |
United States Patent
Application |
20140108032 |
Kind Code |
A1 |
Hufford; Michael ; et
al. |
April 17, 2014 |
CLINICAL MONITORING DEVICE WITH TIME SHIFTING CAPABILITY
Abstract
The present invention is designed to develop research protocols
for clinical trials. The invention can track and enhance subject
compliance with a research protocol. The invention further provides
evaluability data related to subject performance in the clinical
trial. According to an alternative embodiment of the invention, a
portable electronic device is used to query and collect data from
the subject.
Inventors: |
Hufford; Michael; (Chapel
Hill, NC) ; Peterson; David; (Scotts Valley, CA)
; Paty; Jean; (Pittsburgh, PA) ; Shiffman;
Saul; (Pittsburgh, PA) ; McClelland; Jonathan;
(Morgan Hill, CA) ; O'Keefe; Kevin Dennis;
(Gilroy, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Hufford; Michael
Peterson; David
Paty; Jean
Shiffman; Saul
McClelland; Jonathan
O'Keefe; Kevin Dennis |
Chapel Hill
Scotts Valley
Pittsburgh
Pittsburgh
Morgan Hill
Gilroy |
NC
CA
PA
PA
CA
CA |
US
US
US
US
US
US |
|
|
Family ID: |
47391494 |
Appl. No.: |
13/953503 |
Filed: |
July 29, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13603035 |
Sep 4, 2012 |
8533029 |
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13953503 |
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|
13399150 |
Feb 17, 2012 |
8433605 |
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13603035 |
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13211133 |
Aug 16, 2011 |
8145519 |
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13399150 |
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09825533 |
Apr 2, 2001 |
8065180 |
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13211133 |
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Current U.S.
Class: |
705/2 |
Current CPC
Class: |
G16H 10/20 20180101;
G16H 20/00 20180101; G06Q 10/10 20130101; G16H 40/63 20180101; G06Q
10/0639 20130101 |
Class at
Publication: |
705/2 |
International
Class: |
G06F 19/00 20060101
G06F019/00 |
Claims
1. A clinical monitoring device comprising: a clock, wherein the
clock comprises a time and date of the clinical monitoring device
as the clinical monitoring device executes a protocol based on a
trial that defines a predetermined time and date for scheduled
elements and events in the trial to occur, and wherein the time and
date of the clock determine an operational state of the clinical
monitoring device; a data recording software including computer
executable code for: (a) collecting a first health data set from a
subject or a clinician during a first time range and a second
health data set from the subject or the clinician during a second
time range, at least one of the second health data set and the
second time range being determined in part based on a content of
the first health data set, wherein the first and second time ranges
are part of the protocol based on the trial; (b) recording the
first and second health data sets in a computer readable medium;
and (c) including a time and date with the recorded health data
sets received in the computer readable medium; a data input feature
for receiving the health data sets from the subject or the
clinician; and a display having a screen for displaying information
corresponding to an operational state of the device.
2. The device of claim 1, further comprising a time software with
computer executable code to allow, when activated, an adjustment of
the clock from a first event in the protocol, corresponding to a
first operational state of the device, relative to a second event
in the protocol, corresponding to a second operational state of the
device, the device operating at the second event of the protocol in
the same manner to collect health data from the subject or
clinician in the same manner as if the device had reached the
second event without intervention by the time software and
resulting in initiation of a second operational state of the
device; wherein the time software further contains executable code
that does not allow adjustment of the date and/or time to alter an
operational state of the device to move to the second event in the
protocol when the time software is not initiated; wherein
adjustment of the clock from the first event in the protocol to the
second event in the protocol changes an operational state without
modification to the trial.
3. The device of claim 1 or 2, wherein the computer executable code
for collecting the first and second sets of health data includes
computer executable code to collect diary entries.
4. The device of claim 1 or 2, wherein the computer executable code
for collecting the first set of health data during the first time
range and the second set of health data during the second time
range includes computer executable code to determine the first and
second time ranges that correspond to a time of day or a time
period relative to an event.
5. The device of claim 2, wherein the time software with computer
executable code to allow an adjustment of the clock includes
computer executable code to adjust an operating time and date of
the device by selecting an event instead of specifying an actual
time.
6. The device of claim 2, wherein the time software with computer
executable code to allow an adjustment of the clock includes
computer executable code to set the second event in the protocol to
a specific event relative to a time range during which the subject
or clinician is allowed to enter health data.
7. The device of claim 2, wherein the computer executable code to
allow an adjustment of the clock includes computer executable code
to set the clock of the clinical monitoring device to a specific
event in a schedule of a clinical treatment.
8. The device of claim 2, wherein the computer executable code to
allow an adjustment of the clock includes computer executable code
to set the second event in the protocol to a point in time selected
as a result of a calculation based on health data collected prior
to the second event in the protocol.
9. The device of claim 1 or 2, wherein the data recording software
includes computer executable code for providing the protocol with a
plurality of decision points, and wherein the device executes one
or more of the decision points based on health data received from
the subject or clinician.
10. The device of claim 1 or 2, wherein the computer executable
code for collecting the first and second sets of health data
includes computer executable code to collect a diary completed by
the subject or clinician.
11. The device of claim 1 or 2, wherein the computer executable
code for collecting the first and second sets of health data
includes computer executable code to collect a questionnaire
completed by the subject or clinician.
12. The device of claim 1 or 2, wherein the computer executable
code for collecting the first and second sets of health data
includes computer executable code to collect a response of the
subject or clinician to a clinical event.
13. The device of claim 2, wherein the computer executable code to
allow an adjustment of the clock includes computer executable code
for displaying a screen requiring a response from the subject or
clinician.
14. The device of claim 13, wherein the computer executable code
for displaying the screen requiring a response from the subject or
clinician provides a questionnaire for completion by the subject or
clinician.
15. The device of claim 13, wherein the computer executable code
for displaying the screen requiring a response from the subject or
clinician provides a report for completion by the subject or
clinician.
16. The device of claim 13, wherein the computer executable code
for displaying the screen requiring a response from the subject or
clinician includes a request for confirmation of a clinical
event.
17. The device of claim 13, wherein the computer executable code
for displaying a screen requiring a response provides a request for
a subjective response of the subject or clinician to a clinical
event.
18. The device of claim 2, wherein the time software further
comprises computer executable code for selecting the second event
for use in training a user of the clinical monitoring device.
19. The device of claim 2, wherein the time software further
comprises computer executable code for selecting the second event
for use in testing an application of the clinical monitoring
device.
20. The device of claim 2, wherein the computer executable code to
allow an adjustment of the clock of the clinical monitoring device
includes computer executable code to allow advancing an operating
time and date of the clinical monitoring device.
21. The device of claim 2, wherein the computer executable code to
allow an adjustment of the clock of the clinical monitoring device
includes computer executable code to allow adjusting an operating
date and time of the clinical monitoring device to an earlier
operating date and time of the clinical monitoring device.
22.-40. (canceled)
Description
REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. Utility
application Ser. No. 13/603,035, filed Sep. 4, 2012, which is a
continuation-in-part of U.S. Utility application Ser. No.
13/399,150, filed Feb. 17, 2012, now U.S. Pat. No. 8,433,605, which
is a continuation patent application of U.S. Utility application
Ser. No. 13/211,133, filed Aug. 16, 2011, now U.S. Pat. No.
8,145,519, which is a continuation patent application of U.S.
Utility application Ser. No. 09/825,533, filed Apr. 2, 2001, now
U.S. Pat. No. 8,065,180; the subject matter of this application
relates to the patent application titled "Apparatus and Method for
Prediction and Management of Subject Compliance in Clinical
Research", U.S. patent application Ser. No. 09/825,534, now U.S.
Pat. No. 6,879,970, also filed on Apr. 2, 2001; the aforementioned
applications, and the references cited therein, are incorporated
herein by reference in their entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to conducting clinical trials.
Specifically, the invention relates to research protocol
development, management of subject behavior and distribution of
evaluability data.
BACKGROUND OF THE INVENTION
[0003] Noncompliance with research protocols can be especially
problematic, potentially resulting in unusable trial data.
Typically, subjects are given a paper-based diary and asked to make
scheduled entries regarding their illness, medication effects, as
well as other data entries recording events as they happen.
Subjects must keep track of the time of day, where they are in the
sequence of events for any given day, and the appropriate
procedures they are to follow across days. Many subjects do not
complete their diaries or complete their diaries long after the
events that are to be logged. Eight studies have examined
compliance rates of these paper diaries by covertly collecting data
about the timeliness of entries. A dramatic difference between
subjects' reported versus actual compliance was observed. Whereas
the paper diaries appeared to indicate high rates of compliance
(88%), the actual rates of compliance were significantly lower
(54%).
[0004] Evaluation of subject compliance with research protocols is
often performed by examining only one variable at a time. Such
evaluation is not empirically derived by quantitative analysis of
existing datasets. Instead the evaluation relies on the
researcher's judgment and biases to determine whether and what type
of corrective action is required. Furthermore, evaluation of
subject compliance with clinical trial protocols has typically not
taken into account the domain of the clinical trial or the
characteristics of the subjects.
SUMMARY OF THE INVENTION
[0005] In one aspect, a clinical monitoring device is provided
comprising a clock, wherein the clock comprises a time and date of
the clinical monitoring device as the clinical monitoring device
executes a protocol based on a trial that defines a predetermined
time and date for scheduled elements and events in the trial to
occur. In some embodiments, the time and date of the clock
determine an operational state of the clinical monitoring device.
In some embodiments, the clinical monitoring device comprises a
data recording software including computer executable code for
collecting a first health data set from a subject or a clinician
during a first time range and a second health data set from the
subject or the clinician during a second time range, at least one
of the second health data set and the second time range being
determined in part based on a content of the first health data set,
wherein the first and second time ranges are part of the protocol
based on the trial; for recording the first and second health data
sets in a computer readable medium; and for including a time and
date with the recorded health data sets received in the computer
readable medium. In some embodiments, the clinical monitoring
device comprises a data input feature for receiving the health data
sets from the subject or the clinician. In some embodiments, the
clinical monitoring device comprises a display having a screen for
displaying information corresponding to an operational state of the
device.
[0006] In some embodiments, the clinical monitoring device further
comprises a time software with computer executable code to allow,
when activated, an adjustment of the clock from a first event in
the protocol, corresponding to a first operational state of the
device, relative to a second event in the protocol, corresponding
to a second operational state of the device, the device operating
at the second event of the protocol in the same manner to collect
health data from the subject or clinician in the same manner as if
the device had reached the second event without intervention by the
time software and resulting in initiation of a second operational
state of the device. In some embodiments, the time software further
contains executable code that does not allow adjustment of the date
and/or time to alter an operational state of the device to move to
the second event in the protocol when the time software is not
initiated. In some embodiments, adjustment of the clock from the
first event in the protocol to the second event in the protocol
changes an operational state without modification to the trial.
[0007] In some embodiments, the computer executable code for
collecting the first and second set of health data includes
computer executable code to collect diary entries. In some
embodiments, the computer executable code for collecting the first
set of health data during the first time range and the second set
of health data during the second time range includes computer
executable code to determine the first and second time ranges that
correspond to a time of day or a time period relative to an
event.
[0008] In some embodiments, the time software with computer
executable code to allow an adjustment of the clock includes
computer executable code to adjust an operating time and date of
the device by selecting an event instead of specifying an actual
time. In some embodiments, the time software with computer
executable code to allow an adjustment of the clock includes
computer executable code to set the second event in the protocol to
a specific event relative to a time range during which the subject
or clinician is allowed to enter health data.
[0009] In some embodiments, the computer executable code to allow
an adjustment of the clock includes computer executable code to set
the clock of the clinical monitoring device to a specific event in
a schedule of a clinical treatment. In some embodiments, the
computer executable code to allow an adjustment of the clock
includes computer executable code to set the second event in the
protocol to a point in time selected as a result of a calculation
based on health data collected prior to the second event in the
protocol.
[0010] In some embodiments, the data recording software includes
computer executable code for providing the protocol with a
plurality of decision points, and wherein the device executes one
or more of the decision points based on health data received from
the subject or clinician.
[0011] In some embodiments, the computer executable code for
collecting the first and second sets of health data includes
computer executable code to collect a diary completed by the
subject or clinician. In some embodiments, the computer executable
code for collecting the first and second sets of health data
includes computer executable code to collect a questionnaire
completed by the subject or clinician. In some embodiments, the
computer executable code for collecting the first and second sets
of health data includes computer executable code to collect a
response of the subject or clinician to a clinical event. In some
embodiments, the computer executable code to allow an adjustment of
the clock includes computer executable code for displaying a screen
requiring a response from the subject or clinician. In some
embodiments, the computer executable code for displaying the screen
requiring a response from the subject or clinician provides a
questionnaire for completion by the subject or clinician. In some
embodiments, the computer executable code for displaying the screen
requiring a response from the subject or clinician provides a
report for completion by the subject or clinician. In some
embodiments, the computer executable code for displaying the screen
requiring a response from the subject or clinician includes a
request for confirmation of a clinical event. In some embodiments,
the computer executable code for displaying a screen requiring a
response provides a request for a subjective response of the
subject or clinician to a clinical event.
[0012] In some embodiments, the time software further comprises
computer executable code for selecting the second event for use in
training a user of the clinical monitoring device. In some
embodiments, the time software further comprises computer
executable code for selecting the second event for use in testing
an application of the clinical monitoring device.
[0013] In some embodiments, the computer executable code to allow
an adjustment of the clock of the clinical monitoring device
includes computer executable code to allow advancing an operating
time and date of the clinical monitoring device. In some
embodiments, the computer executable code to allow an adjustment of
the clock of the clinical monitoring device includes computer
executable code to allow adjusting an operating date and time of
the clinical monitoring device to an earlier operating date and
time of the clinical monitoring device.
[0014] In another aspect, a method of operating a clinical
monitoring device is provided, the method comprising: (a)
collecting in the clinical monitoring device a first health data
set from a subject or clinician during a first time range and a
second health data set from the subject or the clinician during a
second time range, at least one of the second health data set and
the second time range being determined in part based on a content
of the first health data set, wherein the first and second time
ranges are part of a protocol, wherein the protocol is based on a
trial; (b) recording the first and second health data sets in the
clinical monitoring device; and (c) including a time and date with
the recorded health data sets.
[0015] In some embodiments, the method further comprises initiating
a time shifting mode that allows a user of the clinical monitoring
device to adjust an operating date and time of the clinical
monitoring device from a first event in the protocol, corresponding
to a first operational state of the clinical monitoring device,
relative to a second event in the protocol, corresponding to a
second operational state of the clinical monitoring device, the
clinical monitoring device operating at the second event in the
protocol in the same manner and collecting health data from the
subject or clinician in the same manner as if the clinical
monitoring device had reached the second event without intervention
by the user and resulting in initiation of the second operational
state of the clinical monitoring device. In some embodiments,
adjustment of the operating date and time of the clinical
monitoring device from the first event in the protocol to the
second event in the protocol changes an operational state of the
clinical monitoring device without modification to the trial.
[0016] In some embodiments, collecting the health data sets
includes collecting diary entries. In some embodiments, the
collecting in the clinical monitoring device the first health data
set and the second health data set includes determining the first
and second time ranges that correspond to at least one of a time of
day or week, and a range relative to an event.
[0017] In some embodiments, initiating the time shifting mode that
allows the user of the clinical monitoring device to adjust the
operating date and time of the clinical monitoring device includes
the user adjusting the operating date and time of the clinical
monitoring device by selecting an event instead of specifying an
actual time. In some embodiments, initiating the time shifting mode
that allows the user of the clinical monitoring device to adjust
the operating date and time of the clinical monitoring device
includes setting the second event in the protocol to a specific
event relative to a time range during which the subject or
clinician is allowed to enter health data. In some embodiments,
initiating the time shifting mode that allows the user of the
clinical monitoring device to adjust the operating date and time of
the clinical monitoring device includes setting the clock of the
clinical monitoring device to a specific event in a schedule of
clinical treatment. In some embodiments, initiating the time
shifting mode that allows the user of the clinical monitoring
device to adjust the operating date and time of the clinical
monitoring device includes setting the second event in the protocol
to a point in time selected as a result of a calculation based on
health data collected prior to the second event in the
protocol.
[0018] In some embodiments, operating the clinical monitoring
device comprises providing the protocol with a plurality of
decision points, and wherein the clinical monitoring device
executes one or more of the decision points based on health data
received from the subject or clinician. In some embodiments, the
collecting in the clinical monitoring device the first health data
set and the second health data set includes computer executable
code for collecting at least one of a diary completed by the
subject or clinician, a questionnaire completed by the subject or
clinician, and a response of the subject or clinician to a clinical
event. In some embodiments, initiating the time shifting mode that
allows the user of the clinical monitoring device to adjust the
operating date and time of the clinical monitoring device includes
setting the second event in the protocol to a time in the protocol
when the clinical monitoring device first causes a screen to be
displayed that requires a response from the subject or
clinician.
[0019] In some embodiments, initiating the time shifting mode that
allows the user of a data recording software to adjust the
operating date and time of the clinical monitoring device to the
second event in the protocol includes allowing the user to advance
the operating date and time of the clinical monitoring device. In
some embodiments, initiating the time shifting mode that allows the
user of a data recording software to adjust the operating date and
time of the clinical monitoring device to the second event in the
protocol includes allowing the user to adjust the operating date
and time of the clinical monitoring device to an earlier operating
date and time of the clinical monitoring device. In some
embodiments, the time shifting mode allows selection of the second
event for use in training the user of a data recording software. In
some embodiments, the time shifting mode allows selection of the
second event for use in testing a data recording software. In some
embodiments, the time software automatically jumps from the first
event to immediately before or at the second event. In some
embodiments, the time shifting mode automatically jumps from the
first event to immediately before or at the second event.
[0020] In some embodiments, the clinical monitoring device is a
portable electronic device capable of displaying information and
receiving and storing input from a user, and wherein the portable
electronic device further comprises a tactile alarm electrically
coupled to the portable electronic device to prompt the user to
provide the input to the portable electronic device.
[0021] In some embodiments, the clinical monitoring device is a
portable electronic device capable of displaying information to the
subject and receiving input from the subject and storing the input,
wherein the method further comprises accepting the input from the
subject and activating a tactile alarm if the input is not
correct.
[0022] The goal of clinical trials is to collect valid, reliable
data on one or more conditions within a clinical trial group of
subjects. Subjects in clinical trials are assigned tasks related to
treatment and data collection in accordance with a research
protocol. The integrity of clinical trials rests upon subjects'
faithful performance of these tasks. If subjects fail to comply
with the protocol, the trial will fail to yield reliable, valid
trial data or results. Thus, subject noncompliance in clinical
trials is a significant risk and cost to the pharmaceutical
industry. Accordingly, the creation of appropriate research
protocol, management and enhancement of subject behavior and
effective distribution of clinical trial data is of substantial
value to clinical research.
[0023] The benefits of a system that can track and enhance subject
compliance in a clinical trial include: reliable, valid data;
increased statistical power, reduced clinical trial costs through
smaller sample sizes; reduced time to complete the clinical trial;
and, ultimately, reduced time to get a drug or medical device to
market.
[0024] According to one embodiment of the invention, a method of
protocol development for a clinical trial is provided. The method
includes the steps of identifying a clinical trial target
reflecting a goal of the clinical trial, determining desired
evaluability data categories to be gathered pertaining to a
participant in the clinical trial, wherein an evaluability data of
at least one of the evaluability data categories is used to
determine the desirability of retaining the participant in the
trial or incorporating the participant in one or more of the trial
results.
[0025] According to another embodiment of the invention, a method
of determining preferred targets for subject compliance is
provided, having the steps of providing at least one of the group
of historical subject compliance data and historical protocol data
and generating at least one preferred compliance threshold by
quantitative analysis of at least one of the group of the
historical subject compliance data and the historical protocol
data.
[0026] Another embodiment of the invention provides a method of
monitoring subject compliance and having the steps of providing
historical subject compliance data, generating at least one
algorithm reflective of the historical subject compliance by
quantitative analysis of the historical subject compliance data and
the historical protocol data, translating the at least one
algorithm into at least one decision rule for analyzing subject
compliance information, obtaining the subject compliance
information, comparing the subject compliance information to the at
least one decision rule to determine if corrective action is needed
and prompting corrective action if the step of comparing indicates
that corrective action is needed.
[0027] Another embodiment of the invention provides a method of
determining subject compliance and having the steps of providing
historical subject compliance data and historical protocol data,
generating a spectrum of compliance representative of the
historical subject compliance data not compliant with the
historical protocol data by quantitative analysis of the historical
subject compliance data and the historical protocol data, obtaining
subject compliance information, comparing the spectrum of
compliance to the subject compliance information to determine if
corrective action is needed, and prompting corrective action if the
step of comparing indicates that corrective action is needed.
[0028] Another embodiment of the invention provides a method of
predicting subject noncompliance and having the steps of providing
historical subject compliance data, generating at least one
predictive algorithm for predicting subject noncompliance by
quantitative analysis of the historical subject compliance data,
translating the at least one predictive algorithm into at least one
prediction rule, obtaining subject compliance information,
comparing the subject compliance information to the at least one
prediction rule to determine if action is needed, and prompting
action if the step of comparing indicates that action is
needed.
[0029] A further embodiment of the invention provides a method of
enhancing subject compliance and having the steps of providing
historical subject compliance data, generating at least one
algorithm by quantitative analysis of the historical subject
compliance data, translating at least one algorithm into at least
one decision rule, obtaining subject compliance information and
comparing the subject compliance information to the at least one
decision rule to determine if affirmative action is warranted.
[0030] A further embodiment of the invention provides a compliance
monitoring device for use in clinical trials, having a portable
electronic device capable of displaying information and receiving
and storing input from a user and an alarm electrically coupled to
the portable electronic device and having varying alarm tones,
wherein the varying alarm tones are emitted by the alarm if the
user does not comply with a predetermined protocol for providing
the input to the portable electronic device.
[0031] A further embodiment of the invention provides a compliance
monitoring device for use in clinical trials, having a portable
electronic device capable of displaying information and receiving
and storing input from a user and an alarm electrically coupled to
the portable electronic device and having a tactile alarm.
[0032] A further embodiment of the invention provides a compliance
monitoring device for use in clinical trials, having a portable
electronic device capable of displaying information and receiving
and storing input from a participant in the clinical trial, wherein
the portable electronic device examines the input and reviews the
input for inconsistencies.
[0033] A further embodiment of the invention provides a compliance
monitoring device for use in clinical trials, having a portable
electronic device capable of displaying information and receiving
and storing input from a participant in the clinical trial, wherein
the portable electronic device increases an amount of prompting of
the input from the participant upon an automated determination that
the participant does not comply with a predetermined protocol for
providing the input to the portable electronic device.
[0034] A further embodiment of the invention provides a compliance
monitoring device for use in clinical trials, having a portable
electronic device capable of displaying information and receiving
and storing input from a participant in the clinical trial, wherein
the portable electronic device decreases an amount of prompting of
the input from the participant upon an automated determination that
the participant has reported a predetermined number of events other
than in response to the prompting by the portable electronic
device.
[0035] A further embodiment of the invention provides a compliance
monitoring device for use in clinical trials, having a portable
electronic device capable of displaying information and receiving
and storing input from a user, wherein the user is provided
feedback based on the determination of whether the user has
followed a predetermined protocol for providing the input to the
portable electronic device.
[0036] A further embodiment of the invention provides a medium
suitable for use in an electronic device and having instructions
for execution on the electronic device, the instructions having the
steps of identifying a clinical trial target reflecting a goal of
the clinical trial, determining desired evaluability data
categories to be gathered pertaining to a participant in the
clinical trial, wherein an evaluability data of at least one of the
evaluability data categories is used to determine the desirability
of retaining the participant in the trial or incorporating the
participant in at least one result of the clinical trial.
[0037] A further embodiment of the invention provides a medium
suitable for use in an electronic device and having instructions
for execution on the electronic device, the instructions having the
steps of providing at least one of the group of historical subject
compliance data and historical protocol data and generating at
least one preferred compliance threshold by quantitative analysis
of at least one of the group of the historical subject compliance
data and the historical protocol data.
[0038] A further embodiment of the invention provides a medium
suitable for use in an electronic device and having instructions
for execution on the electronic device, the instructions having the
steps of providing historical subject compliance data, generating
at least one algorithm reflective of the historical subject
compliance data by quantitative analysis of the historical subject
compliance data, translating the at least one algorithm into at
least one decision rule for analyzing subject compliance
information and obtaining the subject compliance information. The
steps further include comparing the subject compliance information
to the at least one decision rule to determine if corrective action
is needed and prompting corrective action if the step of comparing
indicates that corrective action is needed.
[0039] Another embodiment of the invention provides a medium
suitable for use in an electronic device and having instructions
for execution on the electronic device, the instructions having the
steps of providing historical subject compliance data and
historical protocol data, generating a spectrum of compliance
representative of the historical subject compliance data not
compliant with the historical protocol data by quantitative
analysis of the historical subject compliance data and the
historical protocol data, obtaining subject compliance information,
comparing the spectrum of compliance to the subject compliance
information to determine if corrective action is needed and
prompting corrective action if the step of comparing indicates that
corrective action is needed.
[0040] A further embodiment of the invention provides a medium
suitable for use in an electronic device and having instructions
for execution on the electronic device, the instructions having the
steps of providing historical subject compliance data, generating
at least one predictive algorithm for predicting subject
noncompliance by quantitative analysis of the historical subject
compliance data, translating the at least one predictive algorithm
into at least one prediction rule, obtaining subject compliance
information, comparing the subject compliance information to the at
least one prediction rule to determine if action is needed and
prompting action if the step of comparing indicates that action is
needed.
[0041] A further embodiment of the invention provides a medium
suitable for use in an electronic device and having instructions
for execution on the electronic device, the instructions having the
steps of providing historical subject compliance data, generating
at least one algorithm by quantitative analysis of the historical
subject compliance data, translating the at least one algorithm
into at least one decision rule and obtaining subject compliance
information and comparing the subject compliance information to the
at least one decision rule to determine if affirmative action is
warranted.
[0042] A further embodiment of the invention provides a medium
suitable for use in an electronic device and having instructions
for execution on the electronic device, the instructions having the
steps of displaying information to the participant and prompting
input from the participant, accepting the input from the
participant and decreasing an amount of prompting of the input from
the participant upon an upon an automated determination that the
participant has reported a predetermined number of events other
than in response to the prompting by the portable electronic
device.
BRIEF DESCRIPTION OF THE DRAWINGS
[0043] The foregoing and other objects, features and advantages of
the invention will be apparent from the following description and
apparent from the accompanying drawings.
[0044] FIG. 1 illustrates a system according to an embodiment of
the present invention;
[0045] FIG. 2 provides a functional layout of one embodiment of the
present invention;
[0046] FIG. 3 illustrates a method according to an embodiment of
the present invention;
[0047] FIG. 4 illustrates a method according to an embodiment of
the present invention; and
[0048] FIG. 5 illustrates a method according to an embodiment of
the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0049] The illustrative embodiment of the present invention is
designed to develop research protocols for clinical trials, track
and enhance subject compliance with protocol requirements and
provide evaluability data related to subject performance in the
clinical trial.
[0050] The illustrative embodiment involves an empirically derived
set of algorithms and decision rules to predict, track and enhance
subject compliance with research protocols. The illustrative
embodiment uses algorithms and decision rules to provide an
empirical approach for analysis of different types of subject
noncompliance with research protocols. This actuarial approach to
predicting and managing subject noncompliance with clinical trial
protocols is consistent with empirical research demonstrating the
superiority of actuarial prediction of human behavior as compared
to subjective clinical judgment. According to an alternative
embodiment of the invention, a portable electronic device is used
to query and collect data from the subject.
[0051] As used herein "clinical trial" refers to a broad range of
data collecting activities, including studies directed to
monitoring of one or more conditions within a clinical trial group
of subjects. One such example includes drug trials involving
humans. As used herein "subject" refers to any participant in a
clinical trial, whether or not the subject has any relationship to
a doctor or other medical professional.
[0052] Data "evaluability" refers to the usefulness of the data for
the intended clinical trial purpose. Various factors may affect
data evaluability, principally the circumstances under which the
data was collected and how closely the circumstances with the
research protocol for the specific clinical trial.
[0053] "Trial data" or "clinical trial data" refers to data
gathered for the principle purpose of the clinical trial. For
example, trial data would include pain levels experienced by
subjects in a pain medication clinical trial or craving levels in
an antismoking medication clinical trial.
[0054] "Evaluability data" or "compliance data" or "compliance
info' nation" is data that relates to the circumstances under which
the trial data was collected or other data pertaining to
characteristics of the trial data or other evaluability data. Some
examples include timeliness, consistency with other collected data,
proximity of the data to an expected data range and completeness of
the data.
[0055] "Historical protocol data" includes data specifying the
research protocol of earlier clinical trials. Examples of
historical protocol data can include questions posed to subjects,
frequency of prompting of a subject during various times of the day
or week, time allowed for subjects to respond to questions,
requirements of subject behavior, and conditions mandating removal
of a subject from specific analyses or from participation in the
clinical trial.
[0056] As used herein "portable electronic device" refers to any
electronic device that can be adapted for use by a subject and/or
clinical staff for viewing and/or inputting information.
Preferably, the portable electronic device will also have a visual,
audible or tactile alarm to gain the attention of the subject. For
example, a pager having a vibration alarm may be used as a portable
electronic device. Further examples include, pagers with audible
alarms and/or text messaging capabilities, a laptop computer or a
cell phone. Preferably, according to the invention, a portable
electronic device will be a handheld computer provided with a
display and a data input feature, such as a touch-sensitive screen,
or buttons to enable a subject to respond to questions posed on the
display or to input unsolicited information. Examples of such
portable electronic devices include the Palm Pilot by Palm, Inc or
Windows-based devices running Pocket PC from Microsoft Corporation.
Preferably, the portable electronic device will also be adapted to
communicate with at least one other computer via a wireless
connection or via a wired connection, including the use of a modem
and/or a network, such as a LAN or the Internet.
[0057] According to an embodiment of the present invention, a
system is provided as shown in FIG. 1. A processor 10 is provided
and is adapted to communicate with at least one database 20. As
discussed below, the database preferably stores data related to
subject compliance and associated research protocols. An input
device 30 is also provided to allow the subject or another person
to provide input to the processor 10. The input device 30 may be a
keyboard, a modem or other such device adapted for communication
with the processor. An output device 40 is also preferably provided
to receive and display information from the processor 10. Examples
of output devices 40 include a printer and a monitor.
[0058] In one embodiment of the invention, a portable electronic
device 50 is provided and selectively operatively coupled to the
processor 10. The portable electronic device 50 can also include a
processor and may serve as an alarm, an input device, an output
device, and/or a database.
[0059] In one embodiment, the present invention includes software
that resides on a portable electronic device. Preferably, the
portable electronic device is a handheld portable computer.
[0060] In another embodiment, the present invention includes
software that resides on a server. Optionally, the server may
communicate with a computer or portable electronic device.
[0061] FIG. 2 provides a functional layout of an embodiment of the
present invention. Protocol development 200 involves a review of
the goals of the clinical trial to determine research protocol
including subject compliance targets prior to the start of the
clinical trial. Preferably, compliance targets are developed in
accordance with the invention disclosed in the co-pending patent
application titled "Apparatus and Method for Prediction and
Management of Subject Compliance in Clinical Research", Attorney
Docket No. IVQ-001. Optionally, protocol development 200 can
involve analysis of and updates to the protocol while the clinical
trial is underway. Therefore, in accordance with an optional
embodiment of the present invention, protocol development 200 can
occur during trial execution 400.
[0062] The present invention preferably involves identification of
compliance targets relevant to specific features of the research
protocol prior to the start of the clinical trial. These compliance
targets can then be used to track subject compliance. Once these
compliance targets have been identified, compliance-enhancing
features can optionally be developed for a specific clinical trial
and can preferably be incorporated into the functionality of the
portable electronic device.
[0063] It is also within the scope of the present invention to use
empirically derived algorithms to determine the best compliance
targets for a specific clinical trial by the use of the
quantitative analysis methods of the patent application titled
"Apparatus and Method for Prediction and Management of Subject
Compliance in Clinical Research", Attorney Docket No. IVQ-001.
These algorithms could identify non-intuitive, combinations of
variables derived from historical data from previous clinical
trials. Combinations of different compliance targets identified
from other clinical trials could be used to predict a set of
variables to be tracked in order to maximize an ability to detect
subject noncompliance. Preferably, algorithms are translated to
decision rules to ease detection of subject noncompliance.
[0064] Examples of various types of data that may be collected
according to an embodiment of the invention include variables that
may represent `non-intuitive` predictors such as: gender of the
subject, disease severity, the time of the year, and the day of the
week.
[0065] Protocol development 200 preferably includes compliance
feature design 300 to incorporate features into the research
protocol to enhance subject performance in complying with the
research protocol. Compliance features are preferably active during
the execution of the clinical trial. Compliance features may be
provided by a portable electronic device driving the protocol for
subjects by guiding the subject through the protocol, not requiring
the subject to remember the details of all the research protocol.
For example, the portable electronic device can activate an alarm
to prompt the subject to view the device. The portable electronic
device can then prompt the subject to answer appropriate questions
to gather information as specified by the research protocol.
Optionally, the portable electronic device can modify and tailor
questions based on information provided by the subject or based on
input from the clinical staff. Preferably, each subject is provided
with a portable electronic device and will keep the portable
electronic device in their possession at all times during the
clinical trial.
[0066] By the use of the portable electronic device, the present
invention also allows subjects to administer self-reports of trial
data including subjective reports, such as pain reduction,
objective symptom reporting, such as bowel movement or asthmatic
episode and cognitive measures, such as arithmetic tasks or
reaction time. The electronic device may also optionally be
configured to synchronize with any portable physiological
measurement device to gather data from, or communicate with, the
physiological device.
[0067] Moreover, portable electronic devices can optionally track
all aspects of their use, resulting in a comprehensive record of
subject compliance with the research protocol. A preferred
embodiment of the invention allows clinical trial staff to
systematically collect data regarding subject compliance by
tracking a variety of different components of compliance, as well
as check in compliance against empirically derived algorithms and
decision rules of compliance. These empirically derived algorithms
and decision rules allow the disclosed invention to examine the
data for nonintuitive and complex combinations of predictors to
proactively determine whether the observed pattern of interaction
with the portable electronic device suggests noncompliance. The
patent application titled "Apparatus and Method for Prediction and
Management of Subject Compliance in Clinical Research", Attorney
Docket No. IVQ-001 provides additional detail regarding such
algorithms and decision rules.
[0068] The portable electronic device also preferably conducts
ongoing compliance checks and gives the subject feedback about
their performance. For example logical psychometric or other
inconsistencies can be determined by the portable electronic
device. Actions of the portable electronic device are preferably
processed according to decision rules. The portable electronic
device can also vary its behavior based on the subject's behavior.
For example, prompt frequency may be delayed or increased, or
louder prompts may be provided. Also, vibration or visual alerts
can be generated. Evaluability data related to the activity
conducted with a portable electronic device is preferably
transferred from the portable electronic device to a database for
collecting information from multiple portable electronic devices.
Such a database is preferably, a database hosted at a central
location. In one embodiment of the invention, the database is
hosted on PC-based server software and is preferably adapted for
communication with other computers. Additional compliance checks
are preferably performed on the server and feedback is given to
subjects by clinical trial staff; the feedback could be
face-to-face or remote. Finally, the evaluability data is used to
determine the evaluability of subject data, and screen out subjects
or parts of subjects' data during the data analysis and reporting
of the clinical trial data or results. Thus, the present invention
is preferably utilized from beginning to end of a clinical
trial.
[0069] Compliance feature design 300 includes standard features
310, trial specific features 320, and evaluability needs 330.
Incorporating standard features 310 within the research protocol
preferably involves review of historic data from previous research
340, including prior operations of the invention on earlier
clinical trials and other sources of data involving subject
compliance and, preferably, associated research protocols.
Preferably, standard features 310 incorporated into the protocol
will be derived in accordance with co-pending patent application
titled "Apparatus and Method for Prediction and Management of
Subject Compliance in Clinical Research", Attorney Docket No.
IVQ-001, and will involve historic data from related clinical
trials. For example, a clinical trial related to a cardiovascular
condition will preferably develop standard compliance features 310
from historic data involving cardiovascular clinical trials.
[0070] Many types of compliance enhancing features are possible.
For example, to enhance subject compliance with regular monitoring
of symptom severity, varying alarm tones could be used to engender
compliance. For example, if subjects are prompted using an audible
`beep` to complete a symptom report, the tone may increase in
volume and/or pitch to increase the probability that subjects will
complete the report. Other examples of compliance-enhancing
features include allowing subjects to delay a report if they are
busy. Subjects can also initiate a brief suspension of monitoring
if their activity precludes completion of a report, for example,
while driving. The portable electronic device could automatically
re-initiate monitoring after a set amount of time has elapsed, or
alternatively the subject could re-initiate monitoring. These
examples do not represent an exhaustive list of compliance
enhancing features of the present invention.
[0071] According to a preferred embodiment of the present
invention, the following data is gathered by the use of a portable
electronic device: the number of completed assessments or the ratio
to expected assessments; the number or percent of prompts from the
portable electronic device for data input that were not replied to
by the subject; a variety of time based variables, such as for
example, a sleep/wake cycle, obtained by having the portable
electronic device record when subjects went to sleep and awoke each
day of the clinical trial; the amount of time a subject puts the
portable electronic device in a suspend mode that temporarily
prevents the diary from prompting the subject for a reply; how
often and for how long subjects respond to a prompt by requesting
the portable electronic device delay a reply period; the frequency
with which a subject abandons the portable electronic device, for
example, how often does the subject's pattern of inactivity with
the portable electronic device suggest he/she has ceased complying
with the research protocol.
[0072] Trial specific features 320 may also be included in
compliance feature design 300 and may include specific aspects
related to the current clinical trial. For example, compliance
targets can also be identified based on specific characteristics of
the disease state or clinical judgment of the clinical staff. For
example, if subjects typically report a certain number of disease
episodes per day, the present invention may target episodes per day
as one variable to be tracked during the clinical trial and will
automatically prompt subjects if a disease episode is not reported
every 5 hours.
[0073] Evaluability needs 330 may also be incorporated in
compliance feature design 300 and may involve tailoring compliance
features in order to maximize evaluability data or address specific
sponsor requirements. Preferably, evaluability needs 330 will be an
integral part of the initial design of the research protocol. An
example of an evaluability need 330 is a requirement that subject
must report at least 5 disease episodes per day to be included in a
particular analysis. In this example, how many disease episodes
reports each day may be identified as an important variable to be
tracked during trial execution.
[0074] During and/or after trial execution 400, compliance tracking
500 is performed and involves analyzing subject behavior data and
comparing it to the research protocol. Compliance tracking data,
e.g. evaluability data, is gathered during the clinical trial and
compared to historic norms 510 during or after the clinical by the
use of decision rules. Additional detail is provided in the patent
application titled "Apparatus and Method for Prediction and
Management of Subject Compliance in Clinical Research", Attorney
Docket No. IVQ-001.
[0075] According to a further embodiment of the invention,
algorithms can be used with decision rules to automatically
generate feedback to both subjects and research staff. For example,
an algorithm predicting a pattern of intermittent noncompliance
with one facet of a clinical trial protocol could trigger a prompt
to the subject on the portable electronic device to remain
vigilant. Feedback could also be generated to the research staff to
address an issue with the subject. Because the algorithms and
decisions are preferably based on formal, empirical, and
quantitative criteria, subjectivity can be removed from these
decisions, which in turn minimizes the potential for bias.
[0076] An embodiment of the present invention preferably tracks
compliance with the research protocol expected of subjects, such as
timely completion of reports and compliance with the medication
regimen. To successfully assess and remediate subject performance
in clinical trials, the present embodiment preferably tracks
compliance at several levels. If a portable electronic device is
used for data entry, compliance may be tracked at the moment of
data entry by determining whether or not the entry falls within
acceptable parameters of the protocol. For example, is a response
to a prompt required to be completed in the morning timely, or is
the response delayed until the afternoon. Compliance tracking can
also examine the content of the data entry itself to determine
whether or not the subject is being compliant with the research
protocol. For example: inconsistencies among two or more responses
given; subject claiming they are in their living room and
swimming
[0077] Compliance tracking can also take place over some span of
time, such as for example, weekly, to examine patterns or rates of
noncompliance over time. Compliance tracking can also be performed
against data pertaining to the subject's behavior during the
clinical trial. For example, trends in subject response times or in
the responses themselves can be determined
[0078] The present invention can optionally reduce the burden on a
non-compliant subject in order to increase compliance rates by
providing fewer prompts for information. Also, the present
invention can reduce the number of prompts for a subject that has
provided voluntary, unprompted information. In summary, the present
invention can be interactive. The present invention is preferably
configured to initially enhance compliance while evaluating
compliance as the clinical trial progresses. Preferably, the
present invention dynamically adjusts in response to the subject's
behavior, in accordance with the decision rules.
[0079] Compliance feedback 600 may involve forwarding messages,
activating alerts or taking some other action in order to provide
information to the subject 610, the clinical trial staff, including
the research site 620, or to the sponsor 630. Such messages may be
include, for example positive feedback, corrective feedback or a
recommendation to dismiss a subject from the clinical trial.
[0080] To increase the benefit of the compliance tracking feature
of the present invention, compliance feedback is preferably
provided to subjects, the research site, and the clinical trial
sponsor in a timely fashion. Compliance tracking and compliance
feedback may be conducted in an ongoing, timely manner on the
portable electronic device itself. Compliance tracking and
compliance feedback can occur also occur later, after data has been
transmitted to a database, such as a database on a central server.
In such a case, compliance feedback instructions can be sent back
to the portable electronic device to provide feedback to subjects.
Feedback for subjects can optionally be directed to clinical trial
staff for delivery to the subjects.
[0081] According to an embodiment of the invention, a portable
electronic device or a computer, such as a workstation or a server,
can automatically check incoming data against a decision rule to
determine if the pattern of responses require that a compliance
alarm be triggered. Optionally, other demographic variables can
also be checked by a decision rule. If one or more decision rules
note that a problematic pattern of noncompliance or potential
noncompliance is being observed, a number of actions may be taken.
Examples of such actions include: posting a message on a website to
be reviewed by the sponsor or research site, sending an e-mail or
other type of notification, such as an automated call, to the
subjects or research site coordinator, instructing the portable
electronic device to display a certain message to the subject,
instructing the portable electronic device to call the site during
the subject's next interaction with the device, etc. These checks
can either be triggered manually or automatically upon receipt of
the data from the field.
[0082] According to an embodiment of the invention, the computer
can perform the compliance analyses of incoming data instead of the
compliance analyses being conducted by the portable electronic
device. For example, the computer can analyze incoming data and
compute the ratio of missed to completed assessments. This would be
appropriate if the method of collection of the data did not
otherwise allow the compliance data to be generated. For example,
such a method of collection may involve written forms or an
instrumented device not capable of computations.
[0083] According to another embodiment of the invention, the
computer can execute more extensive compliance analyses than are
capable on a portable electronic device. For example, more memory
or processing power may be required to use the item response theory
to examine the probability that a series of responses are likely as
compared to an existing database of population norms for a given
measure.
[0084] According to a further embodiment of the invention, the
computer can aggregate a series of assessment data over time within
or between subjects. These aggregated compliance analyses on the
computer allow for greater capacity than may be capable on a
portable electronic device.
[0085] According to an embodiment of the invention, the computer
can provide data to be displayed. Data may be displayed at the
computer itself or be transmitted to another location, such as via
hardwired or wireless access to the computer, including a LAN or
the Internet. The data can be processed to provide a graphical
display to interested parties. Examples of those who may be
interested in viewing the graphical representation of the
compliance data include a site coordinator (who may be interacting
with the subject), a clinical research organization (who may be
responsible for study execution across a number of research
locations), other agencies interested in the collection of the
data, or the sponsor of the research.
[0086] According to another embodiment of the invention, the
computer can provide ongoing aggregation of data across subjects to
speed the time required to combine, clean, and make available final
data.
[0087] The various features of the computer, such as a workstation
or server, of the above embodiments of the invention may be used
individually or in combination.
[0088] Subject changes in behavior in response to compliance
feedback may also be assessed. That is, an embodiment of the
present invention may assess subjects' behavior in response to
feedback regarding their compliance with the research protocol. For
example, the software can detect whether or not subjects have begun
to follow the research protocol more closely as a function of
having received previous feedback about their noncompliance with
the protocol.
[0089] Compliance feedback can take many forms. Compliance feedback
can be given to a subject at varying intervals at any location,
ranging from frequent, timely feedback, to more episodic feedback
based on aggregate measures of compliance. Systematic compliance
feedback may be given to subjects to encourage continued
compliance, remediate poor compliance, or administer rewards to
subjects for their performance.
[0090] Compliance feedback may be given to the clinical trial
staff. To maximize the impact of the compliance system on trial
success, clinical trial staff preferably receives training in the
monitoring and correcting of subject compliance according to the
present invention.
[0091] In one embodiment, the present invention creates customized
graphical summaries of compliance tracking data and produces
standardized reports for delivery of compliance feedback to
subjects, the research site and/or clinical trail staff. Research
sites are instructed on how to give standardized feedback to
subjects in order to remediate poor subject compliance.
[0092] The aggregation of this compliance feedback can optionally
be compiled into subject and clinical trial status reports during
the clinical trial. These reports are for the research site and/or
sponsors, to be used in evaluating the progress of the clinical
trial. These reports contain a summary of subjects' compliance with
research protocol, and therefore are an indicator of data
evaluability.
[0093] Compliance tracking data is timely 520 forwarded as it is
collected to an evaluability database 700. Aggregation of
compliance data enhances evaluation of subjects, prompting
methodologies and research sites. Aggregated compliance data also
allows for subjects to be examined for evaluability analyses. Also,
evaluability data may be incorporated in compliance tracking 500
decisions during the course of a clinical trial. The evaluability
database 700 also can provide additional historic data 710 to be
included in a historic data database 340 upon which further
research protocols are developed, as appropriate. The evaluability
database 700 is also preferably made available to clinical staff
and research sponsors. By making the evaluability database 700
accessible to clinical trial sponsors, sponsors are able to
participate in decision making regarding the management of the
clinical trial as the clinical trial is conducted. Furthermore,
sponsors are able to monitor the progress of a clinical trial as it
proceeds.
[0094] Evaluability data can be gathered in an evaluability
database: a database that contains information relevant to the
evaluability or acceptability of data from each subject.
Evaluability data represents data that is of significant benefit
for clinical trial sponsors. The evaluability database allows
clinical trial sponsors to have timely evaluability data regarding
the quality and consistency of the trial data. An example of trial
data is efficacy data on the impact of the drug or medical device
on the subject.
[0095] In other words, the evaluability data allows clinical trial
sponsors to have data about the quality of the trial data.
[0096] One specific use of the evaluability database is to
determine whether or not a specific subject's data would be used in
an analysis. For example, an analysis may be limited to those
subjects who met minimal criteria for compliance. Another specific
use of the evaluability database is to determine desirable trial
data for a specific subject or among multiple subjects. This use of
evaluability data involves whether or not specific data points
within one or more subjects' trial data would be used in an
analysis. For example, among all subjects, only trial data from
days when compliance met acceptance criteria may be desired. In
each instance, the evaluability data becomes an important and
unique source of information regarding trial data quality in a
clinical trial.
[0097] Evaluability data can be aggregated to create global, as
well as disease and population-specific databases. The result of
this aggregation of evaluability data provides an ability to
predict subject noncompliance in clinical trials. This prediction
ability increases as more evaluability data is available.
[0098] Evaluability data may also be reviewed by clinical trial
staff. The periodicity of the data review could range from weekly
to instantaneous, optionally using wireless technology or a web
site located on the Internet. During the data review, the data can
be checked using algorithms or decision rules to determine whether
the pattern of subject behavior up to that point in the clinical
trial triggers a decision rule, which may therefore recommend a
course of action. Courses of action may include, for example
providing feedback to the subject, the research site, the sponsor
and/or the clinical trial staff The review may examine data over
varying time intervals to determine whether some type of corrective
action is necessary. By the use of the present invention,
evaluability data can be reviewed for critical patterns of factors
related to noncompliance or other events, such as effectiveness of
compliance enhancement measures, ranging from within-day
assessments to patterns extending over many months of
monitoring.
[0099] The portable electronic device is also preferably adapted to
communicate with another computer to allow the clinical staff to
consolidate the data from all subjects in the clinical trial into
one location for review or processing. Preferably, the portable
electronic device will also be adapted to communicate with at least
one other computer via a wireless connection or via a wired
connection, including the use of a modem and/or a network, such as
a LAN or the Internet. For example, by the use of the Internet or a
dial-up modem connection, a subject may submit information from the
portable electronic device to the clinical staff from the subject's
home.
[0100] In another embodiment, a portable electronic device or a
computer is adapted to communicate with clinical trial equipment
used for measuring, monitoring, controlling or recording data or a
process of the clinical trial. Examples of such processes include
administration of medication or monitoring of heart rates. The
portable electronic device or a computer preferably automatically
records desired data for incorporation in the clinical trial data
or compliance data. A further example of clinical trial equipment
is an instrumented bottle cap, which is capable of recording and/or
reporting when a bottle is opened or closed.
[0101] A monitoring device described herein, e.g., a clinical
monitoring device, can comprise a clock, e.g., a digital clock. The
clock can display a value, and the value can be a date and/or time.
The time and/or date of a clock can determine an operational state
of a clinical monitoring device.
[0102] In another embodiment, clock synchronization can be used to
synchronize data from clinical trial equipment used for measuring,
monitoring, controlling or recording data or a process of the
clinical trial with data collected by a computer or portable
electronic device for later analysis.
[0103] A clock in a clinical monitoring device described herein
comprise a time and date of the clinical monitoring device as the
device executes a protocol (schedule). A protocol can comprise
multiple events, and the events can be scheduled at predetermined
intervals. Intervals among events can be regular or irregular. A
protocol can comprise a one, two, or more events. An event can
comprise a prompt to a subject to administer a medical treatment
(e.g., taking a drug), a prompt to enter health data into a device
(e.g., a symptom (e.g., enter pain level, heart rate, blood
pressure), behaviors, psychological state etc.), or a prompt to
engage in an activity (e.g., start an exercise routine). A subject
can be, e.g., a patient or a participant in a clinical trial. An
event can indicate the type of activity that is to occur. An event
can be indicated by a prompt, e.g., an audible sound (e.g., an
alarm), display of an icon on a device, and/or display of text on a
device. A protocol can comprise one or more scheduled elements. A
scheduled element can be an event, a time range, an alarm, or a
repeat interval. A time range can be a period of minutes, hours,
days, weeks, or years. A protocol can have multiple time ranges. In
some cases, a protocol defines a predetermined time and date for
scheduled elements and events in a trial to occur.
[0104] A protocol executed by a clock can be based on a study,
e.g., a clinical trial, or trial. A study, or trial, can define a
predetermined time and date for scheduled events in the trial to
occur. The study, or trial, can be defined by programming a
clinical monitoring device. A protocol can have different phases
(e.g., a screening phase and a treatment phase). In some cases, a
phase can correspond to a state of a clinical monitoring
device.
[0105] A clinical monitoring device described herein can also
comprise data recording software. Data recording software can
include computer executable code for collecting one or more health
data sets from a subject or clinician. For example, a clinical
monitoring device can comprise data recording software including
computer executable code for collecting a first health data set
from a subject or a clinician during a first time range and a
second health data set from the subject or the clinician during a
second time range. At least one of the second health data set and
the second time range can be determined in part based on a content
of the first health data set. The first and second time ranges can
be part of a protocol based on a trial. In some cases, computer
executable code for collecting a first set of health data during a
first time range and a second set of health data during a second
time range includes computer executable code to determine the first
and second time ranges that correspond to a time of day or a time
period relative to an event. A clinician can be a health care
provider.
[0106] Data recording software can also include computer executable
code for recording first and second health data sets in a computer
readable medium. Furthermore, data recording software can include
computer executable code for including a time and date (e.g., a
timestamp) with the recorded health data sets received in a
computer readable medium. In some cases, data recording software
can include computer executable code for providing a protocol with
a plurality of decision points. The decision points can be
conditional. A device can execute one or more of the decision
points based on health data received from a subject or clinician.
For example, a device may move to one event in a protocol based on
one type of response to a question, and may move to a different
event in a protocol based on a different response to the question.
In some cases, a decision point can be executed if a response is
not provided to a question or if an incomplete response is provided
to a question.
[0107] Computer executable code for collecting a first and second
set of health data can include computer executable code to collect
a diary completed by a subject or clinician, to collect a
questionnaire completed by a subject or clinician, or to collect a
response of a subject or clinician to a clinical event. A response
can comprise an answer to a question.
[0108] A clinical monitoring device described herein can also
comprise a data input feature for receiving health data sets from a
subject or a clinician. The data input feature can be a user
interface, e.g., a screen. Moreover, a clinical monitoring device
can comprise a display having a screen. The display having a screen
can be used for displaying information corresponding to an
operational state of the device.
[0109] Methods are provided herein for operating a clinical
monitoring device. The methods can comprise collecting in the
clinical monitoring device a first health data set from a subject
or clinician during a first time range and a second health data set
from the subject or the clinician during a second time range. In
some cases, at least one of the second health data set and the
second time range are determined in part based on a content of the
first health data set. The first and second time ranges can be part
of a protocol, and the protocol can be based on a trial. The
methods can comprise recording the first and second health data
sets in the clinical monitoring device. In some cases, the methods
comprise including a time and date with the recorded health data
sets.
[0110] A clinical monitoring device described herein can comprise
time software with computer executable code. The time software with
computer executable code can allow, when activated, an adjustment
of a clock in a device from a first event in a protocol,
corresponding to a first operational state of the device, relative
to a second event in the protocol, corresponding to a second
operational state of the device. The device can operate at the
second event of the protocol in the same manner to collect health
data from a subject or clinician in the same manner as if the
device had reached the second event without intervention by the
time software, thus resulting in initiation of a second operational
state.
[0111] In some cases, time software contains computer executable
code that does not allow (prevents) adjustment of the date and/or
time to alter an operational state of the device to move to the
second event in the protocol when the time software is not
initiated. For example, time software can comprise computer
executable code that prevents a user (e.g., a subject in a clinical
trial) from using a time shifting feature on a device. In some
cases, time software can be removed or deactivated in a device
before a subject in a trial or study receives the device. In some
cases, only a person authorized to test or validate a device can be
allowed to activate, or turn-on, time software. To restrict access
to time software, time software can be accessed by entry of a code.
Entry of a code can result in display of a password dialog. A user
can be required to enter one or more passwords to access time
software on a device. Entry of one or more correct passwords can
allow access to time software on a device. In some cases, a subject
in a clinical trial or a clinician can activate time software on a
device. In some cases, time software can be activated by tapping an
icon on a screen.
[0112] Access to, or activation of, time software on a device can
be indicated by displaying an icon on a device, displaying text on
the device, and/or generation of an audible sound. An indication
that time software has been activated on a device can be displayed
in the upper left-hand corner, upper right-hand corner, lower
left-hand corner, lower right-hand corner, or center of a display
of the device.
[0113] Adjustment of a clock from a first event in a protocol to a
second event in the protocol can change an operational state
without modification to a trial or study.
[0114] Adjustment of a clock can comprise setting a number spinner
on a display, selecting a date from a calendar, adjusting a time
spinner, spinning a virtual digital clock, entering text, using a
drop-down list. The ability to adjust a clock can be
restricted.
[0115] In some cases, time software with computer executable code
to allow an adjustment of a clock includes computer executable code
to adjust an operating time and date of a clinical monitoring
device by selecting an event instead of specifying an actual time.
Time software with computer executable code to allow an adjustment
of a clock can include computer executable code to set a second
event in a protocol to a specific time relative to a time range
during which a subject or clinician is allowed to enter health
data.
[0116] Computer executable code to allow an adjustment of a clock
can include computer executable code to set a clock of a clinical
monitoring device to a specific time or event in a schedule of a
clinical treatment. In some cases, the computer executable code to
allow an adjustment of a clock can include computer executable code
to set a second event in a protocol to a point in time selected as
a result of a calculation based on health data collected prior to
the second event in the protocol. The calculation can be, e.g., a
statistical analysis of test results. For example, time shifting
can be initiated if subject data indicates that an event should be
scheduled sooner than the event is scheduled in the protocol. In
some cases, a clock can be advanced to 1 min. before a next event
in a protocol, 30 seconds before the next event in a protocol,
immediately before the next event in a protocol, or to (or at) the
next event in a protocol.
[0117] Initiating a time shifting mode that allows a user of a data
recording software to adjust an operating date and time of the
clinical monitoring device to a second event in the protocol can
include allowing the user to advance the operating date and time of
the clinical monitoring device. In some cases, initiating a time
shifting mode that allows a user of a data recording software to
adjust an operating date and time of the clinical monitoring device
to a second event in the protocol includes allowing the user to
adjust the operating date and time of the clinical monitoring
device to an earlier operating date and time of the clinical
monitoring device.
[0118] Computer executable code to allow an adjustment of the clock
can include computer executable code for displaying a screen
requiring a response from a subject or clinician. The screen can
be, e.g., a touch screen. In some cases, computer executable code
for displaying a screen requiring a response from a subject or
clinician provides a questionnaire for completion by the subject or
clinician. Computer executable code for displaying a screen
requiring a response from a subject or clinician can provide a
report for completion by the subject or clinician. Computer
executable code for displaying a screen requiring a response from a
subject or clinician can include a request for confirmation of a
clinical event. In some cases, computer executable code for
displaying a screen requiring a response provides a request for a
subjective response of the subject or clinician to a clinical
event.
[0119] In some cases, time software comprises computer executable
code for selecting a second event in a protocol for use in training
a user of a clinical monitoring device. The user being trained can
be a subject or a clinician. Training making use of the time
shifting mode can be used to show a subject scheduled elements and
events. Time software can comprise computer executable code for
selecting a second event in a protocol for use in testing an
application of a clinical monitoring device. In some cases, testing
can comprise executing an entire protocol in a relatively short
period of time. Computer executable code to allow an adjustment of
a clock of a clinical monitoring device can include computer
executable code to allow advancing the operating time and date of
the clinical monitoring device. The computer executable code to
allow an adjustment of a clock of a clinical monitoring device can
include computer executable code to allow adjusting the operating
date and time of the clinical monitoring device to an earlier
operating date and time of the clinical monitoring device.
[0120] In some cases, testing can be performed by a user. In other
cases, time shifting can be automated. For example, once time
shifting is activated on a device, the device can have a feature
that automatically keeps time shifting to a next prompt for an
event. Activation of automated time shifting can be indicated on a
display of a device, e.g., by a color-change of the display,
presence of an icon on a display of the device, an audible sound,
or text on a display of the device. Automated time shifting can be
deactivated, e.g., by engaging a button on the device or touching
an icon on a touch-display on the device.
[0121] Upon receiving a prompt for an event, a user can make a data
entry, skip to a next event, or end time shifting mode. In some
cases, a clinical monitoring device is a portable electronic device
capable of displaying information and receiving and storing input
from a user. The portable electronic device can further comprise a
tactile alarm electrically coupled to the portable electronic
device to prompt the user to provide the input to the portable
electronic device.
[0122] In some cases, a method of operating a clinical monitoring
device is provided comprising initiating a time shifting mode that
allows a user of the clinical monitoring device to adjust an
operating date and time of the clinical monitoring device from a
first event in the protocol, corresponding to a first operational
state of the clinical monitoring device, relative to a second event
in the protocol, corresponding to a second operational state of the
clinical monitoring device. The clinical monitoring device can
operate at the second event in the protocol in the same manner and
collect health data from the subject or clinician in the same
manner as if the clinical monitoring device had reached the second
event without intervention by the user. The time shifting can
result in initiation of the second operational state of the
clinical monitoring device.
[0123] In some cases, adjustment of the operating date and time of
the clinical monitoring device from the first event in the protocol
to the second event in the protocol changes an operational state of
the clinical monitoring device without modification to a trial.
[0124] In some cases, computer executable code for collecting first
and second sets of health data includes computer executable code to
collect diary entries. Collecting in the clinical monitoring device
the first health data set and the second health data set can
include determining first and second time ranges that correspond to
at least one of a time of day or week, and a range relative to an
event.
[0125] In some cases, initiating a time shifting mode that allows a
user of a clinical monitoring device to adjust an operating date
and time of the clinical monitoring device can include the user
adjusting the operating date and time of the clinical monitoring
device by selecting an event instead of specifying an actual time.
Initiating a time shifting mode that allows a user of a clinical
monitoring device to adjust an operating date and time of the
clinical monitoring device can include setting the second event in
a protocol to a specific event relative to a time range during
which a subject or clinician is allowed to enter health data.
[0126] In some cases, initiating a time shifting mode that allows a
user of a clinical monitoring device to adjust the operating date
and time of the clinical monitoring device includes setting a clock
of the clinical monitoring device to a specific event in a schedule
of clinical treatment. A schedule of clinical treatment can be a
clinical trial.
[0127] Initiating a time shifting mode that allows a user of a
clinical monitoring device to adjust an operating date and time of
the clinical monitoring device can include setting the second event
in a protocol to a point in time selected as a result of a
calculation based on health data collected prior to the second
event in the protocol.
[0128] In some cases, operating a clinical monitoring device
comprises providing a protocol with a plurality of decision points.
The clinical monitoring device can execute one or more of the
decision points based on health data received from the subject or
clinician.
[0129] Collecting in a clinical monitoring device a first health
data set and a second health data set can include computer
executable code for collecting at least one of a diary completed by
a subject or clinician, a questionnaire completed by the subject or
clinician, and/or a response of the subject or clinician to a
clinical event.
[0130] In some cases, initiating a time shifting mode that allows a
user of a clinical monitoring device to adjust the operating date
and time of the clinical monitoring device includes setting the
second event in a protocol to a time in the protocol when the
clinical monitoring device first causes a screen to be displayed
that requires a response from a subject or clinician.
[0131] In some cases, initiating a time shifting mode that allows a
user of a data recording software to adjust an operating date and
time of a clinical monitoring device to the second event in a
protocol includes allowing the user to advance the operating date
and time of the clinical monitoring device.
[0132] Initiating a time shifting mode that allows a user of a data
recording software to adjust an operating date and time of a
clinical monitoring device to the second event in a protocol can
include allowing the user to adjust the operating date and time of
the clinical monitoring device to an earlier operating date and
time of the clinical monitoring device.
[0133] In some cases, a time shifting mode can allow selection of
the second event for use in training a user of a data recording
software. In some cases, a time shifting mode allows selection of
the second event for use in testing a data recording software. In
some cases, time software automatically jumps from the first event
to immediately before or at the second event. The time shifting
mode can automatically jump from the first event to immediately
before or at the second event.
[0134] In some cases, a clinical monitoring device is a portable
electronic device capable of displaying information to the subject
and receiving input from the subject and storing the input. Methods
can further comprise accepting the input from the subject and
activating a tactile alarm if the input is not correct.
[0135] In another embodiment of the invention, a paper form, such
as a case report form, can be used by the subject to record data.
The data can then be entered into a database by the use of a
portable electronic device or other computer at an appropriate
time. Examples of case report forms include hand-written forms and
forms that allow for machine readable marks to be made, enabling
automated scanning of the case report forms during entry of the
data into a computer.
[0136] In an alternative embodiment of the present invention, the
methods of the present invention may be incorporated in
instructions recorded on a medium suitable for use in an electronic
device, such as a computer, computer network server or a portable
electronic device. The medium can include, for example, a hard
disk, RAM medium, diskette, CD-ROM or other optical or magnetic
storage medium. The instructions can optionally be stored on a
server that can be remote from the subject and/or clinical staff
member.
[0137] According to a further embodiment of the invention, a flow
chart illustrating a method of protocol development of the present
invention is set forth in FIG. 3. First, a clinical trial target
reflecting a goal of the clinical trial is identified, step 102.
Next, desired evaluability data categories to be collected during
the clinical trial are determined, step 104. Preferably, the
desired evaluability data categories pertain to a participant in
the clinical trial. Preferably, at least one of the evaluability
data categories is used to determine the desirability of retaining
the participant in the trial or incorporating the participant in
the trial results.
[0138] According to another embodiment of the invention, a method
for determining preferred targets for subject compliance is
illustrated in FIG. 4. First, historical subject compliance data
and historical protocol data are provided, step 122. Next, at least
one preferred compliance threshold is generated, step 124. The
preferred compliance threshold is preferably generated by
quantitative analysis of the historical subject compliance data and
the historical protocol data.
[0139] According to a further embodiment of the invention, a flow
chart illustrating a method of the present invention is set forth
in FIG. 5. First, relevant subject compliance data, and associated
protocol data, reflecting subject compliance with research
protocols in clinical trials is provided, step 142. Subject
compliance data and associated protocol data is preferably stored
in one or more databases 20 and may be gathered from earlier
clinical trials and/or earlier activities of a current clinical
trial. Optionally, only subject compliance data may be stored, as
some applications of the present invention may not require
knowledge of associated historical protocol for use of the subject
compliance data. For example, analysis of response times to
questions may not require knowledge of the maximum permissible time
for subjects to answer questions in earlier clinical trials. An
output of the present invention preferably includes a database to
provide subject compliance data and, preferably, associated
protocol data, for later use by the invention.
[0140] Next, at least one algorithm representative of the subject
compliance data is generated by quantitative analysis of the
compliance data, step 144. Preferably, multiple algorithms are
generated. The present invention involves the application of
statistical and other quantitative methods to screen existing
research data for markers of, e.g. variables related to,
noncompliance with research protocols. Preferably, the subject
compliance data is also reviewed to exclude invalid data. For
example, data reported by one subject that appears to be well
outside a range established by all other subjects can indicate
invalid data.
[0141] Quantitative analysis methods are used to distinguish,
identify, and predict instances of good and poor compliance. The
quantitative analysis methods of the present invention may include,
but are not limited to, application of a variety of statistical and
data mining techniques, such as logistic regression, discriminant
function analysis, classification and regression trees, neural
networks, and multiple linear regression to screen existing data
and derive algorithms to identify markers of noncompliance with
research protocols.
[0142] Once the one or more algorithms of the invention have been
derived from analysis of existing data, the algorithms can be
translated into specific decision rules, step 146. Decision rules
are essentially reformatted algorithms that can be applied to
current subject compliance data to determine whether action is
needed, step 148. Decision rules may determine a threshold of
compliance or a threshold of noncompliance. Optionally, a decision
rule may identify a spectrum of noncompliance, from minor
noncompliance needing only corrective feedback, to significant
noncompliance requiring subject removal from the clinical trial.
Decision rules may be based on the specific dependent variable used
to derive the algorithm or may be based on one or more differing
variables.
[0143] Decision rules may be translated from algorithms that
identify patterns of noncompliance data that are harbingers or
leading indicators of later, more serious, noncompliance. This
would allow early action to be taken based on these indicators.
Such decision rules would typically be in the form of contingencies
or conditions based on early compliance indicators.
[0144] Optionally, translation of algorithms to decision rules may
involve human input or additional factors. For example, balancing
the impact of a decision rule against the focus of the clinical
trial may result in an alteration of the decision rule. For
example, if subjects' heart rates are being monitored, frequency of
prompting or loudness of reminder alerts may be minimized so as not
to artificially raise subject heart rates. Also, clinical staff may
alter decision rules based on their assessment of external factors
outside of the scope of the quantitative analysis. An example may
include providing more alerts to clinical staff instead of directly
to subjects to provide more interaction between clinical staff and
the subjects.
[0145] A decision rule may also be used to predict which subjects
will fail to complete a clinical trial protocol. Therefore, a
decision to rule to drop the subject from the clinical trial, or to
work to improve subject performance, can be made at an early time.
By providing those conducting a clinical trial with early feedback
regarding subject noncompliance with a research protocol, the
present invention improves clinical trial data quality and may
potentially save both time and money by either improving the
compliance of potentially noncompliant subjects or excluding
unimprovable noncompliant subjects early in a clinical trial.
[0146] If action is determined to be needed, action is prompted,
step 150. Examples of various actions include corrective action,
compliance enhancing action, additional prompting of questions,
reduced prompting of questions and sending an alert to the clinical
staff to discuss an issue with the subject.
[0147] Additional detail regarding the method illustrated in FIG. 5
is provided in the patent application titled "Apparatus and Method
for Prediction and Management of Subject Compliance in Clinical
Research", Attorney Docket No. IVQ-001.
[0148] The present invention can yield very high rates of
compliance with real-time, real world data collection by subjects.
In one embodiment, the present invention for clinical trials (a)
builds compliance features and checks into the software that drives
the protocol, (b) tracks and optionally gives feedback regarding
compliance during the trial, and (c) creates evaluability data that
can be used to determine the evaluability of subjects at the end of
the trial. Thus, this invention is a systematic methodology for
timely, including immediate, data processing, summary, and feedback
regarding subject performance in clinical trials.
[0149] These examples are meant to be illustrative and not
limiting. The present invention has been described by way of
example, and modifications and variations of the exemplary
embodiments will suggest themselves to skilled artisans in this
field without departing from the spirit of the invention. Features
and characteristics of the above-described embodiments may be used
in combination. The preferred embodiments are merely illustrative
and should not be considered restrictive in any way. The scope of
the invention is to be measured by the appended claims, rather than
the preceding description, and all variations and equivalents that
fall within the range of the claims are intended to be embraced
therein.
* * * * *