U.S. patent application number 12/103165 was filed with the patent office on 2008-10-30 for method and system for verification of source data in pharmaceutical studies and other applications.
Invention is credited to Michael J. Rosenberg.
Application Number | 20080270420 12/103165 |
Document ID | / |
Family ID | 39888231 |
Filed Date | 2008-10-30 |
United States Patent
Application |
20080270420 |
Kind Code |
A1 |
Rosenberg; Michael J. |
October 30, 2008 |
Method and System for Verification of Source Data in Pharmaceutical
Studies and Other Applications
Abstract
A method and system are described for verifying database entries
against corresponding source data collected at a plurality of
geographically remote field locations. The invention provides an
electronic means of verifying field data in a manner that is
quicker, less labor-intensive and less error-prone as compared with
existing methods. The invention is particularly useful in the
conduct of adaptive clinical trials of pharmaceutical products.
Inventors: |
Rosenberg; Michael J.; (Post
Orange, FL) |
Correspondence
Address: |
PRIEST & GOLDSTEIN PLLC
5015 SOUTHPARK DRIVE, SUITE 230
DURHAM
NC
27713-7736
US
|
Family ID: |
39888231 |
Appl. No.: |
12/103165 |
Filed: |
April 15, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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60958955 |
Jul 9, 2007 |
|
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60926577 |
Apr 27, 2007 |
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Current U.S.
Class: |
1/1 ; 707/999.01;
707/E17.009; 707/E17.032 |
Current CPC
Class: |
G16H 10/20 20180101;
G16H 40/20 20180101; G16H 70/60 20180101; G06F 16/245 20190101;
G06F 16/24578 20190101; G06F 16/215 20190101; G06F 16/2365
20190101; G06F 16/252 20190101 |
Class at
Publication: |
707/10 ;
707/E17.032; 707/E17.009 |
International
Class: |
G06F 17/30 20060101
G06F017/30; G06F 7/04 20060101 G06F007/04 |
Claims
1. A method for performing source data verification as part of a
clinical trial or other process that requires comparison of values
in a database with source data at a plurality of geographically
remote sites according to a set of procedures or parameters, said
method comprising the steps of: (a) accessing a centralized
database containing values representing the final product of source
data that have been collected and/or recorded in the field; (b)
comparing a value in the database with the corresponding source
data; (c) determining whether the database value agrees with the
corresponding source data; and (d) determining whether any queries
have been generated with respect to such value during the period
since the source data were originally collected.
2. The method of claim 1, wherein step (d) further comprises
displaying the audit trail of any changes made to such value since
the time it was first recorded.
3. The method of claim 2, wherein the audit trail comprises a
chronological list of queries generated with respect to such
data.
4. The method of claim 1, wherein the comparing in step (b) is
conducted at the same clinical site where the source data were
first recorded.
5. The method of claim 2, further comprising: (e) if it is
determined according to step (c) that the database value does not
agree with the source data, generating a new query with respect to
such data.
6. The method of claim 5, further comprising: (f) if it is
determined according to step (c) that the database value agrees
with the source data, creating a record that such value has been
verified.
7. The method of claim 6, further comprising: (g) electronically
reporting the audit trail of step (d) or the new query generated in
step (e), along with the data corresponding to such audit trail or
new query, to an entity capable of determining whether the data
require correction or whether procedures or parameters utilized in
conducting said clinical trial or other process require
modification, and (h) providing instructions, based on the reported
data, to (1) correct the data, or (2) follow or modify the
procedures or parameters utilized in conducting said clinical trial
or other process.
8. The method of claim 1 wherein database values in step (a) may
have been changed during the period since the corresponding source
data were originally collected, and wherein each database value
represents the data point that is believed to be most accurate
based on such audit or correction.
9. The method of claim 1, further comprising: (i) prior to
conducting step (b), ascertaining the number of values in the
database with respect to which step (b) needs to be performed; and
(j) based on the number of values ascertained in step (i),
determining when to conduct step (b).
10. A system for performing source data verification as part of a
clinical trial or other process that requires comparison of values
in a database with source data at a plurality of geographically
remote sites according to a set of procedures or parameters, said
system comprising: (a) a centralized database containing values
representing the final product of source data that have been
collected and/or recorded in the field; (b) means for comparing a
value in the database with the corresponding source data; (c) means
for determining whether the database value agrees with the
corresponding source data; and (d) means for determining whether,
during the period since the source data were originally collected,
any queries have been generated with respect to a corresponding
database value.
11. The system of claim 10, wherein the means in paragraph (d)
further comprises means for displaying the audit trail of any
changes made to such value since the time it was first
recorded.
12. The system of claim 11, wherein the audit trail comprises a
chronological list of queries generated with respect to such
data.
13. The system of claim 10, wherein the comparing in paragraph (b)
is conducted at the same clinical site where the source data were
first recorded.
14. The system of claim 11, further comprising: (e) means for
generating a new query with respect to a database value that does
not agree with the corresponding source data.
15. The system of claim 14, further comprising: (f) means for
creating a record that a value has been verified with respect to
any database value that agrees with the corresponding source
data.
16. The system of claim 15, further comprising: (g) means for
electronically reporting the audit trail of paragraph (d) or the
new query generated in paragraph (e), along with the data
corresponding to such audit trail or new query, to an entity
capable of determining whether the data require correction or
whether procedures or parameters utilized in conducting said
clinical trial or other process require modification; and (h) means
for providing instructions, based on the reported data, to (1)
correct the data, or (2) follow or modify the procedures or
parameters utilized in conducting said clinical trial or other
process.
17. The system of claim 10 wherein database values in paragraph (a)
may have been subjected to prior audit or correction during the
period since the corresponding source data were originally
collected, and wherein each database value represents the data
point that is believed to be most accurate based on such audit or
correction.
18. The system of claim 10, further comprising: (i) means for
ascertaining the number of values in the database with respect to
which the means in paragraph (b) need to be utilized; and (j) means
for determining when to utilize the means in paragraph (b), based
on the number of values ascertained in paragraph (i).
Description
[0001] This application claims priority from U.S. Ser. No.
60/926,577, filed Apr. 27, 2007, the disclosure of which hereby is
incorporated herein in its entirety.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The invention relates to how data collected in field
locations, often geographically diverse, is verified as being
accurate. The comparison is made between data that have been
collected, processed, and stored in a centralized location, along
with any corrections or updates made since the data were first
recorded, against original source data in the field. These steps
are needed to verify the accuracy of data in the centralized
database. Data refers to any information, including measurements,
recordings, verbal responses, images (such as x-rays or CT scans),
laboratory data, output from analyzers, or any other source,
including electronic, paper, or other means.
[0004] Increasingly, clinical research is also under constraints to
improve the ability to manage complex clinical trials, which are
generally geographically diverse. Doing so requires continuous
measurement of numerous performance indices, an easy reporting
mechanism, and the ability to intervene or otherwise change
processes, practices, or other elements to improve performance.
[0005] 2. Description of the Related Art
[0006] Studies performed as part of evaluation of pharmaceutical
products rely on different forms of data collected in the field,
all of which must be accurately handled during collection,
processing, and updating. It is therefore highly desirable, and may
be required, that each piece of data that serves as the basis for
analyzing the results of research, must accurately reflect field
data. In pharmaceutical research, the first time a piece of data is
recorded, it is considered "source," or the correct value. Any
research, whether pharmaceutical or not, must have analyses based
on data that are a true and accurate representation of such source
data, and any group or individual conducting research must assure
that data have been recorded and processed accurately and, when
changes are made between the time data are first recorded and
entered in the final database, that each step does not introduce
errors. This is generally accomplished by comparing data in the
final database against "source" data, which may be defined as the
location in which a piece of data was first recorded.
[0007] Pharmaceutical research is generally conducted in hospitals,
clinical, physician offices, and other medical locations in which
source data may reside in patient's charts, which may be electronic
or paper. Current systems of data entry fall into two general
categories: most (about 50 to 60% of current clinical studies)
involve recording a value on a paper Case Report Form ("CRF"),
after which it is entered by a data entry clerk or the like, who
types each value into an electronic system. A second verification
entry ("double key entry") is then performed as a quality check.
The other means of data entry, currently employed by approximately
40 to 50% of clinical trials, involves web-based Electronic Data
Collection. This generally involves using a Worksheet onto which
data are copied from source data (or "Source"), and from which the
data then are keyed into an electronic system at the site.
[0008] In addition to the integrity of clinical data, data about
the data themselves (meta-data) are useful and highly desirable
means of measuring the practical aspects of how studies are
conducted. These meta-data include site performance metrics such as
error rates on data submitted, enrollment rates, and other elements
key to the timely performance of each site and for the study
overall. These data may be analyzed in different fashions,
including point estimates, trends over time, or relative to other
sites or performance measures and are described in U.S. Ser. No.
60/926,577.
[0009] The ability to analyze clinical data (and corresponding
meta-data) is important and increasingly time sensitive, in part
because the ability to produce more rapid decisions is based on the
rapid availability of accurate data. This capability lies at the
heart of adaptive clinical research, techniques and processes by
which data and meta-data can be continuously reviewed and
incorporated into changes in how studies are conducted. (In the
context of the present invention, "adaptive" means that the course
of such clinical investigations could be altered based on
experience as a study progresses. Close monitoring of performance
metrics allows early identification of weaknesses and allows these
to be addressed, providing a more effective management system.)
These changes may be, but are not limited to, study design, such as
number or allocation of subjects, or to operational elements such
as how to track performance of study sites or interviewers, subject
recruitment strategies, and allocation of resources such as
management.
[0010] Currently verification of site data is performed in one of
two ways. The first is for data to remain at the site until a field
monitor (also known as a "Clinical Research Associate" or "CRA")
visits the site, at which time data are manually reviewed, errors
that are detected are corrected on the scene, and data are then
brought to a centralized location for data entry and computerized
checking for range (allowable values), consistency (if one answer
constrains answers that may appear elsewhere), and possibly other
checks.
[0011] This method, however, has serious drawbacks in that such
data and the corresponding meta-data typically are not available
for weeks to months after they are actually generated, presenting
serious obstacles to being able to measure elements such as site
performance with sufficient time to allow effective management and
seriously hampering, to the point of effectively precluding, the
application of adaptive techniques to either strategic study
elements or to the effective management of the study itself. This
also creates considerably more work for clinical sites, since
discrepancies are identified a long period of time after they are
actually made, and the same mistakes may continue to occur in the
interim. In addition, any errors that are identified require
substantially more effort to go back and correct, since they
occurred weeks ago, and paperwork already has been filed.
[0012] The second possibility is that data are submitted after they
are generated, but before a monitoring visit has occurred. Under
this scenario, data are entered and validation checks applied,
usually at a centralized location. At some time after the data are
received and validated (usually several weeks, but sometimes as
long as several months), the monitor returns to the site to check
each value in the centralized database against source data.
[0013] In either scenario, preparation for such a field visit
occurs by printing out the database values, and printing a separate
list of changes that occurred during the time between when a data
point was first entered and the entry of its final value in the
database. In practical terms, this often amounts to printing out
several hundred sheets of paper, transporting these printouts to a
clinic or other location where patients are seen, and comparing
each value on the paper with a separate paper record of changes
against the original ("source") data. This process is laborious,
time-consuming, and error prone, since large stacks of paper are
difficult to handle, sheets can be lost, and errors noted with
follow-up flags (e.g., "Post-It Notes" or "stickies") can be lost
because they are hidden from sight, fall off, or shift. Errors of
omission can occur under such circumstances and often go
undetected, since there is no backup mechanism whereby such errors
would be suspected or detected. Each discrepancy that is noted
results in an individually-written note (a "query">) that must
be transmitted to the site and also tracked as a change so that an
"audit trail" is maintained. (An audit trail typically comprises a
list of entries, each containing an old value, a new value, an
identification of the person who changed the value, and the reason
for the change.) The queries are generally returned to the site by
fax. The entire process is time-consuming and similarly prone to
error.
[0014] In either of these scenarios, a considerable amount of time
is also required to prepare for a site visit and to enter the
results of site work following the visit. In the first case, the
field monitor has no guidance about where or what kind of errors
might exist and may review several thousand fields during a typical
monitoring visit. Remaining vigilant for errors during such a
review is tedious and difficult, and field monitors with differing
levels of experience may produce dramatically different results.
Preparing for a field monitoring visit generally requires a day of
preparation that includes printing out several hundred sheets of
paper to prepare for a two-day site monitoring visit.
[0015] Thus, it would be desirable to be able to verify field data
more promptly, and in a less labor-intensive and error-prone
manner.
SUMMARY OF THE INVENTION
[0016] The above-identified shortcomings of the prior art are
remedied by the present invention, which provides an electronic
means of organizing, checking and comparing data, and writing and
tracking discrepancies with respect thereto, as well as maintaining
a corresponding audit trail. This system, coupled with the ability
to transmit data and meta-data to a centralized site immediately
after they are generated, greatly reduces the interval between when
data are collected and when "clean" data are available for analysis
and decision making. This facilitates both the strategic aspects of
conducting adaptive trials (i.e., changing study design while in
progress, such as number of patients, treatment assignment, or
other aspects) as well as the tactical aspects (such as assessing
and managing study progress through tracking performance indicators
such as meta-data, an essential part of the adaptive process). In
addition, the invention replaces much of the work presently done by
hand with a uniform, standardized electronic process, improving its
efficiency and enabling it to be utilized equally well when applied
by highly experienced managers and field monitors as by those with
considerably less experience. Finally, the invention's ability to
perform these tasks by electronic means markedly improves the speed
and accuracy of the process of checking source data and in
identifying, recording, and resolving discrepancies that do
occur.
[0017] As an example of time savings in preparing for a site visit,
this tool allows a full copy of the database to be downloaded and
prepared within minutes--a fraction of the time currently
required.
[0018] Comparison of source with recorded data is easily achieved
by the invention's ability to easily navigate all pages of a CRF.
For any page, data recorded on that page can be called up, along
with a record of any change made since the data were first entered
(i.e., the audit trail). In a preferred embodiment of the
invention, these data are provided with a status indicator, where
fields that are unmonitored have a blank checkbox. After data in
the database, as reflected by the computer screen, is compared with
the source and determined to be correct, a check is placed in the
box through clicking the computer mouse on the checkbox. In
addition, individual fields with queries outstanding are marked in
red, for example, since source verification cannot be performed on
such fields where data are still being processed. Discrepancies
between source and recorded data can be identified quickly and
fagged for clarification in a query that is returned to the site
for resolution. The inventive system thus provides a very quick and
effective means of generating and tracking queries that are in a
uniform format that facilitates query management across monitors
and sites. This capability makes it far easier for site personnel,
since every query they receive will be in a standardized
format.
[0019] Thus, in a first embodiment of the invention, a method and a
corresponding system are provided for performing source data
verification as part of a clinical trial or other process that
requires comparison of values in a database with source data at a
plurality of geographically remote sites according to a set of
procedures or parameters. The invention includes: [0020] (a)
accessing a centralized database containing values representing the
final product of source data that have been collected and/or
recorded in the field; [0021] (b) comparing a value in the database
with the corresponding source data; [0022] (c) determining whether
the database value agrees with the corresponding source data; and
[0023] (d) determining whether any queries have been generated with
respect to such value during the period since the source data were
originally collected, in which case the type and frequency of
errors can help the monitor take steps to ensure that such errors
are not repeated (through instruction, training, comparison with
other sites, or other measures) or to determine why errors persist
after one or more queries have been issued and addressed by the
site.
[0024] In an additional embodiment of the invention, step (d)
further includes displaying the audit trail of any changes made to
such value since the time it was first recorded.
[0025] In a further embodiment, the invention includes: (e) if it
is determined according to step (c) that the database value does
not agree with the source data, generating a new query with respect
to such data.
[0026] In another embodiment, the invention includes: (f) if it is
determined according to step (c) that the database value agrees
with the source data, creating a record that such value has been
verified.
[0027] In yet a further embodiment, the invention includes: [0028]
(g) electronically reporting the audit trail of step (d) or the new
query generated in step (e), along with the data corresponding to
such audit trail or new query, to an entity capable of determining
whether the data require correction or whether procedures or
parameters utilized in conducting said clinical trial or other
process require modification; and [0029] (h) providing
instructions, based on the reported data, to [0030] (1) correct the
data, or [0031] (2) follow or modify the procedures or parameters
utilized in conducting said clinical trial or other process.
BRIEF DESCRIPTION OF THE DRAWINGS
[0032] FIG. 1 is a flow chart depicting the operation of the source
data checking process, depicting a preferred embodiment of a
clinical trials system according to the invention.
[0033] FIG. 2 depicts a Microsoft Windows.RTM. dialog box,
customized according to the invention, to perform site
monitoring.
[0034] FIG. 3 depicts a secondary Windows.RTM. dialog box that may
be used, as a preformatted Query Template in accordance with the
invention, to create a query with respect to a discrepancy in a
particular data field shown in FIG. 2.
[0035] FIG. 4 depicts an example of an audit trail, as may be
displayed through the dialog box shown in FIG. 2 or FIG. 3.
DETAILED DESCRIPTION OF THE INVENTION
[0036] Clinical trials are generally highly complex processes that
involve collection of many thousands of data elements from multiple
clinical sites, laboratory facilities, regulatory agencies, and
often outside vendors such as companies supplying test drugs. Many
of the foregoing may be in different countries, which present the
challenges of different cultures, languages, time zones, and other
differences that complicate the ability to effectively manage such
diverse participants in a clinical evaluation. The quality of the
data collected in such circumstances is of paramount importance,
because accurate data are necessary to demonstrate the efficacy and
safety of any pharmaceutical product being evaluated. Failure to
optimize data quality slows study progress; requires a greater
number of patients in order to demonstrate an effect; impairs the
ability of a manager to change a study based on what already has
occurred in the course of the study; and slows regulatory filings
because of additional time required to assure "clean" data.
[0037] A preferred embodiment of a computerized system for source
data verification according to the invention is shown in FIG. 1,
wherein certain functions 1 are performed at a central location,
before a monitor leaves to visit a participating site. Other
activities 2 are performed while the monitor is at the specific
site, and additional activities 3 can be performed at any site with
access, through the internet or other means, to the central
database; these typically include the clinical site, a hotel or
other access point while traveling, or after the monitor returns to
his/her office at the central location. The measurement of
performance metrics also then may be accomplished 4 at a
centralized location from which study activities are
coordinated.
[0038] The process by which the invention is utilized is also shown
in FIG. 1 and begins with downloading 5 the portion of data in the
central database that pertains to the site(s) to be visited. This
downloading typically occurs while the monitor is at the central
location. A separate capability of the invention allows the number
of unmonitored data fields to be continually reviewed with respect
to each distinct site, so that management staff can determine when
a site visit is justified. This also assists with predicting and
scheduling resources such as field monitors and allows an adaptive
approach to monitoring in that stronger or more experienced
personnel can be sent out when a greater amount of data have
accumulated that need to be source verified, while less capable
monitors might visit when smaller amounts of data have
accumulated.
[0039] At the site, the monitor begins by opening a tree view of
data that exist from the particular site. This lists each patient
in the study, each visit, and each CRF (or "form") completed at
each of the visits. The monitor selects 6 a visit and a form, and
may select a particular data field in the form. In a preferred
embodiment of the invention shown in FIG. 2, the invention shows
the variable name, description, value in the database, and
verification status for each data field in the form. In FIG. 2, the
tree view showing each patient, visit, and form is displayed in the
left pane 1 of the Windows.RTM. dialog box. After a particular
visit is selected, each variable on the form selected is displayed,
along with the variable name, description, value, and verification
status in the upper right pane 2. If any changes have been made to
the data since the time they were submitted, each change is
chronologically noted in the lower right pane 3, facilitating
tracking of changes. Lower right pane 3 also provides separate
"buttons" that can call up the full text of a specific CRF question
("Question Details") or the details of an existing or previous
query ("Audit Trail Details"). A menu 4 at the top of the dialog
box provides tools for navigation among a site's patients in the
study, and among the various visits and forms for each patient, and
also provides access to Query Templates, Notes, Help, and other
tools and aids.
[0040] The invention also displays when an active query exists with
respect to a particular field, in which case source verification
cannot be performed until the active query is resolved. (In the
preferred embodiment shown in FIG. 2, outstanding queries are
indicated by a Question Mark symbol immediately to the left of the
variable name in upper right pane 2 of the dialog box.)
[0041] Referring now back to FIG. 1, each value in the database
then is physically compared 7 with the Source (accounting for any
changes that may have occurred since submission), to determine
whether the data are in agreement. If the Source agrees with the
CRF value, the monitor marks the data as verified 8. As shown in
FIG. 2, the verification status ("Verified") field in pane 2 has a
box that is unchecked if verification has not been completed, and
is checked if the data are in agreement. Moreover, if certain
fields are not available for verification (for example, if a query
is outstanding, as described above), this also is indicated in the
"Verified" field, for example, by a red circle with an X through
the middle. (When those queries are resolved and the corresponding
data are eligible to be source verified, the status change is
indicated by the appearance of an unchecked box in the "Verified"
field.)
[0042] Continuing in FIG. 1, if queries have been generated since
the data were originally submitted, each query is listed in
chronological order (i.e., the Audit Trail is displayed) 9 so that
the monitor can track each change. A representative example of such
a list appears in FIG. 2, in lower right pane 3. In this instance,
it can be seen that three queries have been issued regarding the
highlighted data field in pane 2. Clicking on each of these reveals
details, including the individual who initiated the query, the
date, and the nature of the question, as shown in FIG. 4.
[0043] Regardless whether queries previously have been generated
with respect to a particular data field, if there currently is
disagreement between the Source and the CRF value in such data
field, a query now must be generated. In this case, the monitor
selects the discrepant field (as shown, for example, in FIG. 2),
selects a button to create a query and, in a new dialog box that
opens as a preformatted Query Template (see, for example, FIG. 3),
enters the value from the source document. Thus, as shown in FIG.
1, a query summarizing the discrepant results thus is automatically
generated 10 using preformatted Query Templates, modifying each as
necessary for the circumstances.
[0044] The process in FIG. 1 continues with a determination 11 of
whether the visit is completed. If the visit has not been
completed, the monitor selects 6 another visit and form (or another
data field in the form previously selected), and repeats the
process described in the foregoing paragraphs. It should be noted
that the present invention also has the ability, at any point in
the process, to call up electronic notes that may be appended to
any field.
[0045] If the visit has been completed, updated data (which may
include new queries, status of verification, notes) are normally
uploaded 12 to the centralized database. However, the user can
connect to the centralized database at any time, including during
the course of the site visit, e.g., at a hotel, through a telephone
connection or any other means by which data can be transferred.
[0046] The invention further provides the additional, essential
capability of intervening in response to issues that can be
improved. Knowledge of a problem or issue (based on certain data
collected and verified as set forth in the preceding paragraphs)
sounds an alarm to intervention, which can be implemented through
any conventional manner appropriate to the circumstance and
problem. For example, if it becomes apparent that a single question
on a CRF produces an inordinate number of queries or poor quality
data, the wording of such question can be re-evaluated. If the
clarity of the question can be improved, such question can be
re-worded as appropriate. As another example, if the data somehow
indicate that an individual site is having problems, the invention
enables a site monitor or project manager to "drill down" in order
to better understand the source of such problems. Thus, the site
monitor or project manager may detect from the data that one
particular interviewer has a higher query rate than others at such
site or elsewhere within the study. In that case, it is possible
for the manager to intervene to determine whether the problem is
one of inadequate training, time, or other factors with respect to
such interviewer.
[0047] Thus, continuing in FIG. 1, following upload 12 of the
primary data, performance metrics may be created and/or updated 13,
based on the primary data, to reflect most recent experience. The
immediacy of such data is key to the notion of modifying trials in
progress, either by strategic measures (which critically depend on
very quick availability of accurate data) or tactical measures,
such as query rates, response times, screening and enrollment
measures. The latter are particularly important to being able to
modify suboptimal performance, and similarly depend on timely
measurement and availability of such metrics.
[0048] In a preferred embodiment, the invention enables a "Site
Performance Index" as an overall measure of the respective sites'
abilities to measure quality of data. This Index may include
various measures such as query rate, time to respond to queries,
and other measures that can together form a simple, convenient
measure of how well the various sites perform, and thus guide
oversight efforts. For each site, this information is compared
against average values for all sites, and each field monitor can
continuously track this as a key performance indicator.
[0049] The foregoing description details certain embodiments of the
invention. It will be appreciated, however, that the invention can
be practiced in many ways. It also should be noted that the use of
particular terminology when describing certain features or aspects
of the invention should not be taken to imply that the terminology
is being re-defined herein to be restricted to including any
specific characteristics of the features or aspects of the
invention with which that terminology is associated. The scope of
the invention should therefore be construed in accordance with the
appended claims and any equivalents thereof.
* * * * *