Download Paper-less Reporting: Online Data Review and Analysis Using SAS/PH-Clinical Software

Paper-less Reporting:
On-line Data Review and Analysis Using SAS/PH-Clinical® Software
Eileen Ching, SmithKline Beecham Pharmaceuticals, Collegeville, PA
Rosemary Oakes, SmithKline Beecham Pharmaceuticals, Collegeville, PA
ABSTRACT
REPORTING OF CLINICAL TRIALS
The paper presents the applications of SAS/PHClinical in clinical trials reporting and analysis, and
describes how clinical researchers can utilize its
capabilities to analyze and explore the information
with timeliness and efficiency during the drug
development process.
The reporting of clinical trials involves collection,
review, and analysis of immense amount of data.
Most of the data is captured on paper case report
forms which is then entered into a database.
Usually when the clinical scientist wants to examine
data while the trial is ongoing, he/she must obtain
either case report form copies or data listings from
another group. Any queries or summarization of
data must be performed by the programming and
statistical staff.
If new study populations or
parameters are called for, then the programming
staff must modify existing or develop new programs
which cause delays in the review of result.
Ordinarily, the study results are printed out and
delivered as stacks of paper. Reports are not
readily accessible from a user's desktop. Integrated
reporting frequently requires the development of
new programs because the existing software can not
be easily used with the combined data.
Since it is essential to extract useful information
from the vast amount of data collected, statistical
report generation is a representative and usually
time-consuming activity in the world of clinical
research and development. SAS/PH-Clinical, a
data review and analysis tool developed by SAS
Institute, provides the functionalities of a data
browser, a query builder, as well as a flexible
reporting system that is capable of creating
templates which users can invoke and customize in
a visual interface environment. Instead of receiving
and reviewing reports printed on stacks of paper, the
clinical scientists can view them on-line within the
same system that is used for the generation of those
displays.
SAS/PH-CLINICAL
In addition, the paper discusses how a subset of an
organization's internal reporting system can readily
be developed into a Computer-assisted New Drug
Application (CANDA). Coupled with concepts of
data warehousing, practical and beneficial data
querying and report generation tools can greatly
shorten the development time and improve the
quality of a drug submission.
Among the many efforts in the development of online reporting tools, SAS Institute has released
SAS/PH-Clinical software (most recently version
2.03) which specializes in clinical reporting. The
developers of this product are currently working with
sponsor companies to enhance the functionality of
this product.
SAS/PH-Clinical provides the
capabilities of a data browser, a query builder, as
well as a flexible reporting system that is capable of
creating templates which users can invoke and
customize in a graphical interface environment.
INTRODUCTION
In the world of clinical research and development,
vast amounts of data are collected for the support of
clinical development plans. Currently, this is mostly
a paper-based process.
New tools are being
developed by sponsor companies, as well as
software companies, to provide on-line clinical data
review and analysis in a user-friendly environment.
These tools alleviate the cumbersome task of
printing and eliminate the delay in the delivery of
clinical trial analysis results.
STUDY DEFINITION (DATA WAREHOUSING)
A study in SAS/PH-Clinical is defined as a collection
of SAS data sets. These data sets are not direct
copies of the input database (e.g., Oracle). They
contain data that are usually manipulated to
expedite reporting. The methods of manipulation
may include transposing, collapsing, and complex
mapping of variables. In addition, the resulting data
sets often contain derived and value-added
variables such as age and days relative to start of
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treatment. The variables from the input database
that are not necessary for reporting are omitted.
This reporting database is created based on data
warehousing principles. Data warehouse takes the
by-product transaction data and organize and store
this data so the end-user can access and use it.
Derived data points and summary data is of great
importance to a clinical reviewer or report writer.
Including this data in the reporting database also
reduces complex calculation and data processing in
generating the reports.
DATA BROWSER
Figure 2
Many times clinical has the need to review the raw
data at any time during the clinical trial. SAS/PHClinical provides spreadsheet-like format for easily
viewing raw data. The data is presented with
variables as columns and observations as rows.
Variables from individual data sets can be organized
into variable groups of related data.
Variable
groups are created when the study is defined in
SAS/PH-Clinical. Figure 1 displays an example of
variables and variable groups for selection when
using the data browser. Raw data can be selected
from a group or across multiple groups.
For
example, if the user needs to view adverse
experience (AE) data, he/she might also want to
select certain demographic variables to provide a
more complete picture.
Figure 2 shows
demography data displayed with AE data in the data
browser.
The software provides many useful options in the
data browser that can be customized to individual
preferences. For example, a user can hold or
freeze certain columns so that they always appear
on the screen when scrolling through the remainder
of the columns or one can re-arrange the display
order of the variables. The end-user is also able to
create newly derived variables based on currently
selected data. The browser also provides the ability
to export data to other applications such as EXCEL
and WORD. Another feature of the browser is the
ability to execute simple summarization in tabular or
graphical form. Figure 3 shows an example of a
simple summary created for race. This can be
accomplished effortlessly by press of a button
without any programming support. Once a table of
summary statistics is generated, the user can "drilldown" on a specific cell to see a list of observations
which defines the cell. For example, in a race
distribution table, one can double-click on the "#
Patients" cell to display a list of patients for the
selected race (see Figure 4).
Figure 1
Figure 3
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delivered to clinical report writers in printed
hardcopy. SAS/PH-Clinical provides the ability to
generate and review reports all in the same
environment.
Reports are developed as PHTemplates which consist of writing SAS code and
designing windows with graphical interface. The
code section of a PH-Template contains macro-type
methods of SAS programming.
The graphical
window is the front-end for the user to specify the
parameters needed to run the reports. These
windows contain widgets, such as text boxes, pulldown lists, radio buttons, checkboxes, and
command buttons. All of these widgets enable the
end-users to create their reports in a "point-andclick" fashion with minimal effort.
Using PHTemplates, the statistical and programming staff
can now write a single program that is flexible
enough to create multiple reports of the same
format. For example, one AE template can be used
to produce summary tables by relationship to study
medication or by AE severity. The same template
can also produce tables containing different subsets
of AEs (e.g., all AEs, those that led to withdrawal,
serious AEs, etc.). An example of a template for AE
summaries is provided in Figure 6.
Figure 4
QUERY BUILDER
In addition to browsing raw data, one may also wish
to perform queries which result in data meeting
certain criteria of interest. These queries can be
easily built without knowledge of any programming
languages. The criteria are defined by the user's
selection of values that are made available by the
system. For example, if the user wanted to view all
adverse experiences for patients 18 years of age
and over, then this query can be specified by
selecting age from a list of variables, a '>=' (greater
than or equal to) from a list of available operators,
and finally entering '18' as the value of comparison
(see Figure 5). Queries can be saved for later use,
especially the more frequently used ones.
Figure 6
LIBRARIES
The PH-Templates and the generated reports can
be saved into libraries. Each library serves as a
central repository for storage and on-line review of
output for a particular reporting effort. Printed
hardcopies are no longer needed for delivery.
Figure 7 shows a library of template objects, and
Figure 8 depicts a library of saved outputs.
Figure 5
TEMPLATE DEVELOPMENT
Traditionally, data summaries and analyses are
generated by programming and statistical staff and
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versatility of PH-Templates enables easy report
creation on integrated data. As a result, less
programming effort is required for an NDA which
shortens the time it takes to prepare a submission.
Moreover, this could lead to overall reduction of
drug approval time.
AREAS FOR IMPROVEMENT
Although SAS/PH-Clinical is equipped with many
powerful features, the pilot programs done at
SmithKline Beecham have discovered some major
areas which require further enhancement in addition
to minor issues. These include:
Figure 7
Figure 8
-
Product administrative tasks need to be
streamlined.
In the current version, users cannot select a
collection of objects and perform the same
operation on them. For example, to create new
version of report objects, each report must be
deleted individually before the replacement
report can be saved. The ability to group
objects to perform tasks such as delete, copy to
another library, and set property privileges is
necessary for efficient reporting.
-
Detached batch processing is essential for a
production system.
The number and size of reports required for
interim and final reporting necessitates
detached processing capabilities.
-
Report template view and print functionality
needs to be improved.
In SAS/PH-Clinical version 2.03, page breaking
is both display- and printer- specific. To view
and print report output with the proper page
breaking, the individual report page layout, the
display monitor, and the specific printer all must
be synchronized. This is a time consuming and
repetitive task.
-
More user-friendly features are needed in the
browser and template building environments.
Certain user preferences set in one session
cannot be saved for another session. Also, the
current settings of toggled switches are not
obvious to the user.
-
The software should allow for study-specifc
formats (e.g., via format search).
Often there are needs to have a study level
format that contains values specific to that
study. This currently is not allowed in the
product.
ELECTRONIC SUBMISSIONS
Presently, many NDAs (New Drug Applications) are
submitted to the FDA (Food and Drug
Administration) in an electronic form.
One
important component of a CANDA (Computer
Assisted New Drug Application) is the data review
and analysis tool. SAS/PH-Clinical has many of the
functionalities required of such a tool and it has
been used by sponsor companies for submissions to
the FDA. Most submissions involve integration
across studies.
Typically, combining multiple
studies means development of new programs and/or
mapping of data into a standard structure. In
SAS/PH-Clinical however, since study definitions
only allow one form of data structure, there is no
longer a need to do additional mapping of data for
an integrated effort. PH-Templates written for a
single study report can be conveniently used for an
integrated report without additional modifications. In
order to generate a report using combined data, one
only needs to open multiple studies. Therefore, the
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All of the issues found from the SmithKline
Beecham experiences have been communicated to
SAS Institute and many of the enhancements
requested will be implemented in the next release of
the software, version 2.10.
TRADEMARK
SAS and SAS/PH-Clinical are registered trademarks
or trademarks of SAS Institute Inc. in the USA and
other countries. ® indicates USA registration.
Other brand and product names are registered
trademarks or trademarks of their respective
companies.
CONCLUSION
SAS/PH-Clinical has many of the capabilities for
paper-less reporting. Currently, with the help and
feedback of sponsor companies, SAS Institute is
continuing to make improvements to this product.
Although there are limitations to the current version,
the system has the potential to be an extremely
useful tool for clinical trials reporting.
AUTHORS CONTACT INFORMATION
Eileen Ching
SmithKline Beecham Pharmaceuticals
1250 South Collegeville Road
PO Box 5089
Collegeville, PA 19426
Phone: 610-917-5056
E-mail: [email protected]
List of Figures
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Variable Groups for a Study
Browser Displaying a Selected
Group of Variables
A Summary of Race Variable
Drill-down of One Race Value
Query Window
PH-Template Custom Window
Folder Containing PH-Templates
Folder Containing Save Output
Objects
Rosemary Oakes
SmithKline Beecham Pharmaceuticals
1250 South Collegeville Road
PO Box 5089
Collegeville, PA 19426
Phone: 610-917-5057
E-mail: [email protected]
BIOGRAPHY
Eileen
Ching
is
a
Clinical
Applications
Programmer/Analyst at SmithKline Beecham
Pharmaceuticals responsible for clinical applications
programming in clinical trials research and
development. Her five years of industry experience
includes SAS-based clinical and statistical reporting,
applications design and development, and various
drug submission support including CANDA project
development.
Rosemary Oakes, a Biostatistician at SmithKline
Beecham Pharmaceuticals, is responsible for input
into clinical study design, statistical programming
and analysis, and interpretation of results for clinical
drug development. Her six years of statistical
experience
includes
statistical
reporting
methodology, SAS macro and report programming,
SAS graphical data presentation, and statistical
support of drug submissions to international
regulatory agencies.
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