In addition, we have developed a communication and management tool; with its help, projects can be planned and supervised, SOPs can be organised and made available, or "merely" document management can be carried out.
As you see, with the help of our internet-based products and services there are numerous ways of optimising the study conduct and data collection, as well as the communication.
I would be pleased if these few lines have aroused your interest and we could have a talk on the phone, or in a personal conversation, about the possibilities of implementing our product solutions in your house, as well as about a possible cooperation.
Data Management Software
ECRON uses Oracle Clinical version 4.0.3 together with TMS 4.0.6 (Thesaurus
Management System) as data management system. Of course, both system components
are 21 CFR Part 11-compliant. SAS system versions 6.12 and 8.2 are additionally
available for data extraction and reporting. Microsoft Windows 2000 Server is
used as operating system of the servers and Windows 2000 Workstation on the client
side. Both systems are currently being migrated to version 4.5 (called OPA 4.5).
Remote Data Capture
ECRON provides the remote data capture option of the Oracle Clinical system. It
allows user-friendly web-based data entry as well as online data validation by
the investigators. Under OPA 4.5 it will be possible to design the case report
form (CRF) directly within the system. This CRF can be printed as a paper CRF
(PDF file) and also be used for electronic data capture. This facilitates conventional
study conduct, purely electronic data management as well as hybrid solutions.
Our key product is the electronic Case Report Form (eCRF), which provides
special features for our customers by integrating medical equipment and electronic
forms. Our range of customer-specific eCRF solutions includes:
RDC guarantees internationally accepted quality of data (based on Oracle Clinical™). Current data capture allows quick reactions predominantly regarding number of patients enrolled, development of key data, SAE documentation etc. Continuous offsite monitoring through direct contact with investigator avoids misunderstandings at an early stage.
Enhanced data quality by immediate entry checks (e.g. completeness, plausibility, within range, correct dates) leads in itself to a drastically reduced load of queries. Remaining queries via electronic communication require less time on-site. Problems become obvious at an early stage and consequently have a positive impact on on-site monitoring.
You never again have the question of a data manager: "illegible"??!! and you find all necessary comments of your investigator at the proper place.
It is well understood that initial training of both investigator (and study nurse,
too) and monitor is mandatory.
We recommend checking the IT-set-up at the centre carefully, since a poor system
may interfere with recruitment rate.
WE OFFER: Highly competitive pricing.
Oracle Clinical Hardware Components
The Oracle system is installed on an application server and a database server
as back-end. All servers are based on Hewlett Packard Netserver with Pentium 3
processors. The application server has 512 MB RAM and the database server has
1 GB RAM. All hard drives are mirrored (RAID 1). Furthermore, all servers are
connected to an uninterruptible power supply (UPS) and they have two independent
power supply units and Ethernet cards. The Oracle Clinical servers are located
in an air-conditioned and locked server room in Frankfurt/M., Germany, together
with other servers of ECRON's company network and network components. The desktop
computers are Intel-based personal computers that are connected to a company-wide
network.
Validation of the Installation
The Oracle installation and the functionality were tested using extensive validation
procedures. The documentation of this validation can be looked at in Frankfurt.
Data Security System Components and Back-up Strategy The Oracle servers and the
file servers are backed up daily (Monday through Friday). The back-up software
used for the Oracle servers allows a hot back-up, i.e. the database does not have
to be shut down for the back-up. A DLT tape streamer (HP SureStore Autoloader)
is used for the data back-up. This streamer can load 9 tapes simultaneously with
up to 80 GB storage capacity per tape. The tapes used on Monday through Thursday
are overwritten every second week using the tape from a Monday only on Mondays,
the tape from a Tuesday only on Tuesdays and so forth up to Thursday. The tape
written on a Friday is denoted as weekly back-up tape and will be stored for 12
weeks, and the last weekly back-up of a month (denoted as monthly back-up) will
be stored for 12 months. The back-up software has an overwrite protection, which
is used on all tapes and guarantees that a tape will not be re-used prior to the
expired period. Weekly and monthly back-ups are stored outside of the company
in a safe. Running in parallel to the back-up to tape process, there is the back-up
to ECRON's NAS (Network Storage Array) whereby another hot back-up of the Oracle
Servers is performed backing up the data directly to ECRON's Berlin site. The
data is transferred over a VPN (Virtual Private Network) whereby the communication
is encrypted and secured with strong authentication methods.
Archiving
As soon as the database can be locked -or, in agreement with the sponsor, during
the ongoing study- all data together with the status of the data cleaning process
will be exported from the Oracle Clinical database and stored on CD ROMs as SAS
datasets. A copy of those CD ROMs will be submitted to the sponsor. Upon request
of the sponsor, the data can also be stored in other file formats.
Global Libraries
Global libraries, which are maintained within Oracle Clinical, guarantee that
reliable and validated modules are used for the database design and for the data
validation process. Modification of active procedures or addition of new modules
to the library requires the agreement of the head of the biometrics department
and of the global librarian, a dedicated member of the data management department.
The maintenance of the global library is done in close cooperation with ECRON
USA, who use a similar installation of Oracle Clinical 4.0.3.
Data Management
Data Management Manual:
ECRON assigns a responsible biometrician and a responsible data manager to each
project. This assignment is valid throughout the entire project. If necessary,
additional employees will be assigned to the project. The responsible data manager
writes a data management manual according to ECRON's SOPs prior to the start of
the data entry. This manual comprises the following items:
The sponsor and ECRON's responsible employees sign that data management manual.
Database Design and Data Transfer:
For standard CRF pages and a number of indications ECRON has established specific
CRF modules. These modules are used for the database design according to ECRON's
SOPs if the sponsor does not provide his own specifications. After the database
is locked, ECRON exports SAS datasets or ASCII files from the database and sends
them to the sponsor using ECRON's standard format. ECRON is prepared to modify
the format of the datasets used for the data transfer according to the specifications
of the sponsor. In this case, test data will be extracted from the Oracle Clinical
database and submitted to the sponsor to ensure that these datasets comply with
the sponsor's specifications and that the sponsor can load these data into their
database. ECRON is also prepared to transfer data to the sponsor on an on-going
basis during the course of the study. This can be done using CD ROMs or e-mails
with PGP encryption.
Test of the Database:
The data manager and the data entry staff verify that every database complies
with the specifications of the sponsor and the biometrician, as laid out in
the data management manual. Furthermore, they check whether the handling of
the data entry screens is user-friendly. Data entry may only start after the
database has passed these checks and the database has been released for the
productive use.
Data Entry:
ECRON enters all data using double data entry with immediate resolution by the
second data entry person. Oracle Clinical supports an automatic review process
with built-in range checks. Missing or implausible numeric and alphanumeric
values are classified. To this end, different categories like, for example,
still missing queries, implausible values and technical failures that can no
longer be verified; values missing without reason after having been reworked
by the investigator; and values missing for special reasons can be used. All
CRF data which are not cleaned automatically will be reviewed once again by
an experienced CRA regarding compliance with the study protocol, completeness
and plausibility.
Coding:
ECRON will carry out the coding of text entries for concomitant diseases (MedDRA),
concurrent medications (WHO-DD including ATC codes), and adverse events (MedDRA).
Dictionaries for the coding other than MedDRA and WHO-DD can be implemented;
they are to be provided by the sponsor. Data Validation Procedures which are
programmed within Oracle Clinical are used to perform the automated data validation.
Data manager and CRAs review the detected discrepancies and decide which discrepancies
can be internally resolved and which discrepancies have to be resolved by the
investigator using query sheets/data clarification forms (DCFs). The DCFs are
generated and tracked using Oracle Clinical. This ensures that all detected
discrepancies will be dealt with. Eyeball checks will be performed in addition
to the automated validation procedures. These checks are focused on text entries
and correlations between data, which require a medical judgement (e.g. adverse
events versus concomitant diseases and concomitant medication). The responsible
data manager checks whether all detected discrepancies have been finally dealt
with and that all eyeball checks have been performed prior to locking the database.
Database Lock:
ECRON locks the database and opens the randomisation code (if applicable) after
all data cleaning measures have been performed, the blinded review meeting has
taken place and the statistical analysis plan has been reviewed. The database
is locked by removing the rights for data modifications in Oracle Clinical,
by exporting the data into SAS datasets, and by storing these data on CD ROM.
Medical Review
ECRON performs an extensive medical review of all collected data if this has
been agreed with the sponsor.
Valid Statement
The valid statement displays the evaluability of each individual patient. Deviations
from the protocol (e.g. trial terminated prematurely, inclusion/exclusion criteria
not satisfied, or non-compliance) are examined for relationship to the study
medication, and weighted. According to this assessment the patients are assigned
to the various evaluation populations:
The valid
statement is reviewed and released at the blinded review meeting prior to unblinding
the study. At least ECRON's responsible data manager, responsible biometrician
and project manager/responsible CRA and a representative of the sponsor take
part in this meeting.
If you would like to receive further information, please contact
Dr Ernst Bluemner at the ECRON Headquarters in Frankfurt/Main
phone +49 (69) 66 80 30-0
fax +49 (69) 66 80 30-29
e-mail ernst.bluemner@ecron.com