Download THECIS-The Clinical Information System

THECIS
The Clinical Information System
Thomas R. Hoffman. Judith A. Burns, Leon T. Hairie
Lederle Labora tori es
THECIS minimizes the setup time required for a
new study in several ways. Variable descriptions are automatically provided for variables
in the THECIS dictionary. This feature not
only eliminates entry of information but also
lets the user know that a variable name entered
has not been used previously. THECIS also takes
into consideration the row and column structure
common to most forms. For example. a case report form designed to collect 15 rows of laboratory test results would require entering only
the information contained in the first row.
The remaining 14 rows of information are automatically added by THECIS. Finally, the SAS
code that is required to set up the database
used for data entry and editing is gen€rated
by THECIS.
INTRODUCTION
Traditional information systems have difficulty
handling the information associated with new
drug research and development. The data that are
collected in clinical studies vary with drug type,
study design. and the current regulatory guidelines. Statistical analyses and reports are not
standardized but change as methodology ;s imr
proved. Database queries often require a substantial programming effort.
Because of these difficulties. most institutions
use the SAS® software package to supplement other
systems. SAS is a powerful tool not only for
statistical analyses, but also for data management, data entry and editing, data storage.
report generation. and graphical displays. However, although SAS provides a method for dealing
with the complex and changing problems associated
with clinical studies. it does not provide a
system for processing clinical data. As a resul~
too much time is spent developing programs to
handle special problems at the expense of time
that should be used for improving methodology.
An even greater concern is the possibility of an
unfound programming error leading to an incorrect
interpretation of the data.
DATA ENTRY
Data can be entered either off-line into a card
image file or on-line directly into a SAS database. For data thdt are entered off-line, the
THECIS code builder generates the program for
loading the data into the SAS database. On-line
entry is simplified by using the display screens
created for each case report form. Optional online edit checks can be used to assist data entry.
This paper describes THECIS, a SAS based clinical
infonmation system under development at Lederle
Laboratories. THECIS is not a SAS product but is
programmed entirely in the SAS language, System
features include: a menu-driven prompting facility. computer assisted data editing, a fullscreen data editor, a program code builder, and
a dated database that can be restored easily to
a previous date.
DATA STORAGE
THECIS uses two levels of data storage, protocol
and drug. The protocol level database is designed for data entry and editing. It is organized similar to the pages in a case report form
booklet. There is a separate dataset for each
form - each dataset contains as many variables
as there are fields on the case record form.
This structure is the most efficient for displaying all information in a case report form on the
same screen.
The following sections of the paper summarize the
main components of THECIS: setting up a new
study, entering data. data storage, computer
assisted edit checks, editing data. and reports!
queries. ,Data security is also discussed. An
ex.ample is given showing how the user interacts
with THECIS.
The drug level database combines data across protocols. It is structured to allow efficient
generation of data display tables and statistical
analyses for individual protocols as well as
across several protocols. This database ;s used
for pooled safety and efficacy analyses as well
as for responding to questions, both from company personnel and regulatory agencies. It is
also useful for data exploration in order to
fonl! objectives for future studies.
SETTING UP A NEW STUDY
Before data from a clinical study can be proce~sed. some ~reparation is necessary.
In THECIS,
thlS pre~aratlon begins when the case report form
booklet lS completed. THECIS provides the user
an input screen for enterin.g the case report
forms used for ea-ch visit of the ·study. If a
form has not been previously usee, the user is
prompted f~r additional descriptive information.
For.each fleld on the form, THECIS requires a
~arlable name and description, and formats for
lnputting and displaying the variable If the
data is to b~ entered Off-line. the r~cord and
col~mn 10catl0n of each variable is required.
A dlsplay screen for entry/editing must also
be created for each new case report form.
Status and update variables are associated with
every observation in both the protocol and drug
level databases. The update variable records
the date when an observation was added or modified. The status variable is used to flag suspect observations and to track changes to the
data.
When an observation in the protocol level database is edited. THECIS moves the current version
393
checks. If changes in the data are required.
the SAS full-screen editor is used to edit the
protocol level database. The screen is formatted similar to the case report form using the
data entry screen that had been created when the
form was designed.
of this observation into an audit database~
before permanently updating the database. This
audit database is identical to the protocol level
database in structure, but only contains the
earlier version of the observations that have
been changed or deleted. The drug level database
is automatically modified to reflect the changes
to the protocol level database.
The THECIS edit menu provides several alternative methods of editing data. If a form number
is specified, all patient data associated with
that form are available for editing. If the
observation number of the record requiring change
is known~ SAS can point directly to this observation. Otherwise, the SAS FIND, LOCATE, or
SEARCH commands can be used to identify the observation. Once displayed on the screen, the
status variable is changed to ICI and the record
is corrected by typing over the incorrect data.
If a format is associated with the variable that
is entered, SAS will decode the entered data.
This feature is particularly useful for coding
data directly on the screen from text contained
on the case report form.
Once all data for a protocol has been released
for final analyses, the dat.a in the protocol
level and audit databases are moved off-line.
However~ an empty database remains on-line in
the case that further errors are detected.
COMPOTER ASSISTED EDIT CHECKS
Many edit checks are automatic, requiring no additional information from the user. THECIS has
already prompted the user for sufficient information to build an empty case report form booklet.
When data are inputted into the protocol level
database, missing forms, missing data within
forms, and variables with values not in the format library, are detected. In addition, since
the page, visit number, and visit date variables
are assumed to be in the same relative order.
they are used to check the internal consistency
of the data for each patient. including duplicate
or unexpected visits.
Alternatively, all data can be displayed for a
selected patient. What ap~ears on the screen is
the computer version of the case report form
booklet. An IADDI option is available for entering data on new patients.
Global changes and deletions also can be made.
For example, if a patient number were incorrectly
entered for a case report form booklet, it could
be corrected in the entire database. using a
simple command.
In order to determine whether all patients are
accounted for. patient enrollment information
must first be entered. An input screen for updating the patient ~nrollment status is available for use by the medical research staff. The
user is prompted for trial and patient numbers.
as well as the screening number, start date, sex.
age, and initials for each patient. In addition
to completing the patient inventory, this patient
enrollment information is used for tracking
studies. Once THECIS knows the starting date
for each patient enrolled. several tracking
reports are available. Graphs can be requested
that compare actual enrollment to the planned
enrollment rate and charts can be requested
showing the number of case report forms booklets
expected and received each week.
When the edit session is complete, a batch job
is submitted that permanently updates the protocol and drug level databases. The original
values of the changed or deleted observations are
moved into the audit database.
REPORTS/QUERIES
As THECIS is currently designed~ ad hoc queries
require an understanding of the drug level database as well as some knowledge of the SAS programming language. This is not a problem for
the data handling groups who are already familiar
with SAS, but will make THECIS less friendly than
desirable to users with minimal computer skills.
To complete the computer assisted editing, information on the allowable data values for each
continuous variable (possible values cannnot be
listed in the format library) needs to be
entered. An input screen is available for
entering minimum and maximum values for an individual variable~ changes from baseline, or a
mathematical function involving several variablcs.
Conditional edit checks can also be specified.
The a~10wab1e values on one variable may depend
on the values of one or more other variables.
For example, if on a medical history form, a
disease is checked as present, then an explanation should also be entered.
However. more standard queries are menu-driven
and require no knowledge of the SAS language.
For examplc, a patient profile can be requested
that combin~s dosage information. adverse experiences, and an optional selection of laboratory tests. This profile can be produced for a
subset of patients based on demographic characteristics. adverse experiences, or laboratory
test abnormalities. These profiles are particularly useful for identifying and clarifying
potential safety problems.
EDITING DATA
DATA SECURITY
The batch program that updates the SAS databases
produces a report summarizing the possible data
errors detected by the computer assisted edit
Three different methods of protecting the databases are used. First~ all databases are write
394
protected. Only the protocol level databases
can be edited, and only by one group of users.
When changes are made. the original version of
the changed observation is stored on-line in
an audit database. Since dates of all transactions are recorded, it is possible to restore
the databases to any previous date. Finally, a
tape backup system each night automatically
cop1es to tape any SAS database that has been
modified during the day.
Two levels of data storage are used to facilitate both data entry/editing and analysis/reporting. The status and update variables assure
that all data is available for preliminary
analyses, but allow suspect data to be removed
before a final analysis.
Data editing is assisted by computer edit checks.
Changes to data are made Dn screens formatted
similarly to the pages in a case report form
booklet. An edit menu is also provided to
assist the user \ldth global edits.
USING THECIS - AN EXAMPLE
Figure 1 shows the menu that is displayed when a
member of the clinical systems group enters the
command ITHECIS·. Option IAFI is chosen each
time a new form has been designed. A model form
code may be entered if the new form is similar
to an existing one. Figure 2 shows the completed
input screen containing information from the case
report form in Figure 3. Note that the heading
information (patient number, date~ etc.) is
standard for all fOnlls and is not entered.
Both on-line and off-line entry are available.
In the latter case~ the SAS code required for
inputting th~ data is automatically generated.
The setup time required to enter specifications
for a new case report form is minimized since
THECIS takes advantage of the row and column
structure common to most forms.
The last card field (shown in the seventh column)
is used to minimize the number of variable names
that are inputted~ For example. although the
variable MH is entered. it will be interpreted
by THECIS as MHl, MH2, •.. , MHIO. The format
field is used to associate an output format
with a variable. If the format name is not recognized by THECIS. the user is prompted to
enter the format information after exiting from
the screen.
THECIS is still under development -- individual
modules of the system are being implemented as
they are completed. The edit module has recently entered the testing phase. Performance
characteristics and user acceptance are not yet
known. However~ the system has been designed
so that modifications can be easily implemented.
This ability to respond to change is made
possible by the power and flexiDility built
into the SAS language.
Option 'AS' [from Figure 1), is next used to
build the edit screen. For case report form
3460, building the screen is a two-step process. Figure 4 shows the input screen after the
first step. The standard heading information is
provided automatically. SAS prompts the user to
identify the location of the variables associated
with the newly entered fields. Note that the
user is required to enter only one row of the
medical history disease infonllation. THECIS
automatically adds the remaining nine rows.
Additiona1 information on THECIS can be
obtained by contacting
rinally~ a menu-driven program library assists
the user to query the drug level database and
to run standard reports.
Thomas R. Hoffman
Lederle Labs
Pearl River, NY 10965
Reference
Hoffman, Thomas R., Burns, Judith A.,
Hairie, Leon T. THECIS The Clinical
Information System. Drug Information
Journal 18[1). 1984.
When the user leaves this screen~ THECIS expands
the screen (see Figure 5) using information from
Figures 2 and 4. The user can now make any final
changes to the screen. In this case, the codes
associated with the ten diseases are entered as
initial values for all observations in the data
set. SAS automatically decodes the values when
the screen is displayed.
SUMMARY
This paper has described how the SAS language can
be used to build a system for managing clinical
information. THECIS is a total system, spanning
from the initial case report form design through
the final reports used for a new drug submission.
Its menu-driven facility provides the means for
all users to communicate with the system and
assures that their requests are accurately
captured and processed.
395
Figure 1
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THECIS
PF2 CONTINUE
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SELECT OPTION:
XX EXIT
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FORM OR Of'
PROTOCOL
FORMS
AF
ADD FORM - ENTER MODEL FORM?
AP
ADD PROTOCOL
MF
MODIFY FORM
MP
MODIFY PROTOCOL
OF
DElETE FORM
DP
DELETE PROTOCOL
BF
BROWSE FORMS OATA SET
BP
BROWSE PROTOCOL DATA SET
SCREENS
STATUS
AS
ADD SCREEN
SS
SESSION STATUS
MODIFY SCREEN
lF
LIST FORMS/SCREENS
ADD SCREEN - BATCH
LP
LIST DRUG/PROTOCOLS
MS
BS
Fi gure 2
STATus:
FORI'1: 3460 DESCRIPTION: DEMOGRAPHIC/MEDICAL HISTORY
VAR NAME VARIABLE DESCRIPTION
======== ==========================
COL
INFORMAT
========
FORMAT
========
FML
PATIENT's INlTIALS
11
$3
$3
AGE
AGE
14
2
2
SEX
SEX
IS
SEX
RACE
RACE
17
RACE
HT
HEIGHT
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WT
WEIGHT
22
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INFORMED CONSENT OBTAINED?
DIS
DISEASE
MH
CONDITION?
15
MHe
PERTINENT DETAILS
16
NEW
DATE: 02SEP83
FIRST LAST
CARD
1
NOYEs
4
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DIS
2
NOYES
2
11
MHe
2
11
S_SYS
SYSTOLIC BP - SITTING
11
3
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S DIAS
DIASTOLIC BP - SITTING
PULSE
14
3
12
17
3
12
PULSE
306
11
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ALLERGIC DISEASES
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ENDOCRINE AND
D
META80llC DISEASES
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NERVOUS.SYSTEM DISEASE
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PULMONARY OISEASE
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RENAL DISEASE
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HEMATOlOGI[; OISEASE
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BLOOD PRESSURE lsotttngl ImmHgl
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397
Figure 4
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STATUS:
»»}}}}}}»}»»»»»»}»»»> FORM
PATIENT'S INITIALS-
AGE·
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ALLERGIC
DRUG ALLERGIES
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ENDOCRINE/METABOLIC
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RACE:
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398
/
/ _ __
WEIGHT:
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