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Computer Application Used in Clinical Trial

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TABLE OF CONTENTS I. INTRODUCTION * II. DEFINITIONS * III. GENERAL PRINCIPLES * IV. STANDARD OPERATING PROCEDURES * V. DATA ENTRY * A Electronic Signatures * B. Audit Trails * C. Date/Time Stamps * VI. SYSTEM FEATURES * A. Facilitating the collection of quality data * B. Facilitating the inspection and review of data * C. Retrieval of Data * D. Reconstruction of Study * VII. SECURITY * A. Physical Security * B. Logical Security * VIII. SYSTEM DEPENDABILITY * A. Systems documentation * B. Software validation * C. Change Control * IX. SYSTEM CONTROLS *
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Page 1: Computer Application Used in Clinical Trial

TABLE OF CONTENTS

I. INTRODUCTION *

II. DEFINITIONS *

III. GENERAL PRINCIPLES *

IV. STANDARD OPERATING PROCEDURES *

V. DATA ENTRY *

A Electronic Signatures *

B. Audit Trails *

C. Date/Time Stamps *

VI. SYSTEM FEATURES *

A. Facilitating the collection of quality data *

B. Facilitating the inspection and review of data *

C. Retrieval of Data *

D. Reconstruction of Study *

VII. SECURITY *

A. Physical Security *

B. Logical Security *

VIII. SYSTEM DEPENDABILITY *

A. Systems documentation *

B. Software validation *

C. Change Control *

IX. SYSTEM CONTROLS *

A. Software Version Control *

B. Contingency Plans *

C. Backup and Recovery of Electronic Records *

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COMPUTERIZED SYSTEMS USED IN CLINICAL TRIALS

I. INTRODUCTION

This document addresses issues pertaining to computerized systems used to

create, modify, maintain, archive, retrieve, or transmit clinical data intended for

submission to the Food and Drug Administration (FDA). These data form the

basis for the Agency's decisions regarding the safety and efficacy of new human

and animal drugs, biologics, medical devices, and certain food and color

additives. As such, these data have broad public health significance and must be

of the highest quality and integrity.

FDA established the Bioresearch Monitoring (BIMO) Program of inspections and

audits to monitor the conduct and reporting of clinical trials to ensure that data

from these trials meet the highest standards of quality and integrity and conform

to FDA's regulations. FDA's acceptance of data from clinical trials for decision-

making purposes is dependent upon its ability to verify the quality and integrity of

such data during its onsite inspections and audits. To be acceptable the data

should meet certain fundamental elements of quality whether collected or

recorded electronically or on paper. Data should be attributable, original,

accurate, contemporaneous, and legible. For example, attributable data can be

traced to individuals responsible for observing and recording the data. In an

automated system, attributability could be achieved by a computer system

designed to identify individuals responsible for any input.

This guidance addresses how these elements of data quality might be satisfied

where computerized systems are being used to create, modify, maintain,

archive, retrieve, or transmit clinical data. Although the primary focus of this

guidance is on computerized systems used at clinical sites to collect data, the

principles set forth may also be appropriate for computerized systems at contract

research organizations, data management centers, and sponsors. Persons using

the data from computerized systems should have confidence that the data are

no less reliable than data in paper form.

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Computerized medical devices, diagnostic laboratory instruments and

instruments in analytical laboratories that are used in clinical trials are not the

focus of this guidance. This guidance does not address electronic submissions

or methods of their transmission to the Agency.

This guidance document reflects long-standing regulations covering clinical trial

records. It also addresses requirements of the Electronic Records/Electronic

Signatures rule (21 CFR part 11).

The principles in this guidance may be applied where source documents are

created (1) in hardcopy and later entered into a computerized system, (2) by

direct entry by a human into a computerized system, and (3) automatically by a

computerized system.

 II. DEFINITIONS

Audit Trail means, for the purposes of this guidance, a secure, computer

generated, time-stamped electronic record that allows reconstruction of the

course of events relating to the creation, modification, and deletion of an

electronic record.

Certified Copy means a copy of original information that has been verified, as

indicated by dated signature, as an exact copy having all of the same attributes

and information as the original.

Commit means a saving action, which creates or modifies, or an action which

deletes, an electronic record or portion of an electronic record. An example is

pressing the key of a keyboard that causes information to be saved to durable

medium.

Computerized System means, for the purpose of this guidance, computer

hardware, software, and associated documents (e.g., user manual) that create,

modify, maintain, archive, retrieve, or transmit in digital form information related

to the conduct of a clinical trial.

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Direct Entry means recording data where an electronic record is the original

capture of the data. Examples are the keying by an individual of original

observations into the system, or automatic recording by the system of the output

of a balance that measures subject’s body weight.

Electronic Case Report Form (e-CRF) means an auditable electronic record

designed to record information required by the clinical trial protocol to be

reported to the sponsor on each trial subject.

Electronic Patient Diary means an electronic record into which a subject

participating in a clinical trial directly enters observations or directly responds to

an evaluation checklist.

Electronic Record means any combination of text, graphics, data, audio,

pictorial, or any other information representation in digital form that is created,

modified, maintained, archived, retrieved, or distributed by a computer system.

Electronic Signature means a computer data compilation of any symbol or

series of symbols, executed, adopted, or authorized by an individual to be the

legally binding equivalent of the individual's handwritten signature.

Software Validation means confirmation by examination and provision of

objective evidence that software specifications conform to user needs and

intended uses, and that the particular requirements implemented through the

software can be consistently fulfilled. For the purposes of this document, design

level validation is that portion of the software validation that takes place in parts

of the software life cycle before the software is delivered to the end user.

Source Documents means original documents and records including, but not

limited to, hospital records, clinical and office charts, laboratory notes,

memoranda, subjects' diaries or evaluation checklists, pharmacy dispensing

records, recorded data from automated instruments, copies or transcriptions

certified after verification as being accurate and complete, microfiches,

photographic negatives, microfilm or magnetic media, x-rays, subject files, and

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records kept at the pharmacy, at the laboratories, and at medico-technical

departments involved in the clinical trial.

Transmit means, for the purposes of this guidance, to transfer data within or

among clinical study sites, contract research organizations, data management

centers, or sponsors. Other Agency guidance covers transmission from

sponsors to the Agency.

III. GENERAL PRINCIPLES

A. Each study protocol should identify at which steps a computerized system will

be used to create, modify, maintain, archive, retrieve, or transmit data.

B. For each study, documentation should identify what software and, if known,

what hardware is to be used in computerized systems that create, modify,

maintain, archive, retrieve, or transmit data. This documentation should be

retained as part of study records.

C. Source documents should be retained to enable a reconstruction and

evaluation of the trial.

D. When original observations are entered directly into a computerized system,

the electronic record is the source document.

E. The design of a computerized system should ensure that all applicable

regulatory requirements for recordkeeping and record retention in clinical trials

are met with the same degree of confidence as is provided with paper systems.

F. Clinical investigators should retain either the original or a certified copy of all

source documents sent to a sponsor or contract research organization, including

query resolution correspondence.

G. Any change to a record required to be maintained should not obscure the

original information. The record should clearly indicate that a change was made

and clearly provide a means to locate and read the prior information.

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H. Changes to data that are stored on electronic media will always require an

audit trail, in accordance with 21 CFR 11.10(e). Documentation should include

who made the changes, when, and why they were made.

I. The FDA may inspect all records that are intended to support submissions to

the Agency, regardless of how they were created or maintained.

J. Data should be retrievable in such a fashion that all information regarding

each individual subject in a study is attributable to that subject.

K. Computerized systems should be designed: (1) So that all requirements

assigned to these systems in a study protocol are satisfied (e.g., data are

recorded in metric units, requirements that the study be blinded); and, (2) to

preclude errors in data creation, modification, maintenance, archiving, retrieval,

or transmission.

Security measures should be in place to prevent unauthorized access to the

data and to the computerized system.

IV. STANDARD OPERATING PROCEDURES

Standard Operating Procedures (SOPs) pertinent to the use of the computerized

system should be available on site.

SOPs should be established for, but not limited to:

! System Setup/Installation

! Data Collection and Handling

! System Maintenance

! Data Backup, Recovery, and Contingency Plans

! Security

! Change Control

DATA ENTRY

A. Electronic Signatures

1. To ensure that individuals have the authority to proceed with data entry, the

data entry system should be designed so that individuals need to enter

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electronic signatures, such as combined identification codes/passwords or

biometric-based electronic signatures, at the start of a data entry session.

2. The data entry system should also be designed to ensure attributability.

Therefore, each entry to an electronic record, including any change, should be

made under the electronic signature of the individual making that entry.

However, this does not necessarily mean a separate electronic signature for

each entry or change. For example, a single electronic signature may cover

multiple entries or changes.

a. The printed name of the individual who enters data should be displayed by the

data entry screen throughout the data entry session. This is intended to preclude

the possibility of a different individual inadvertently entering data under someone

else=s name.

If the name displayed by the screen during a data entry session is not that of the

person entering the data, then that individual should log on under his or her own

name before continuing.

3. Individuals should only work under their own passwords or other access keys

and should not share these with others. Individuals should not log on to the

system in order to provide another person access to the system.

4. Passwords or other access keys should be changed at established intervals.

5. When someone leaves a workstation, the person should log off the system.

Failing this, an automatic log off may be appropriate for long idle periods. For

short periods of inactivity, there should be some kind of automatic protection

against unauthorized data entry. An example could be an automatic screen

saver that prevents data entry until a password is entered.

B. Audit Trails

1. Section 21 CFR 11.10(e) requires persons who use electronic record systems

to maintain an audit trail as one of the procedures to protect the authenticity,

integrity, and, when appropriate, the confidentiality of electronic records.

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a. Persons must use secure, computer-generated, time-stamped audit trails to

independently record the date and time of operator entries and actions that

create, modify, or delete electronic records. A record is created when it is saved

to durable media, as described under "commit" in Section II, Definitions.

b. Audit trails must be retained for a period at least as long as that required for

the subject electronic records (e.g., the study data and records to which they

pertain) and must be available for agency review and copying.

2. Personnel who create, modify, or delete electronic records should not be able

to modify the audit trails.

3. Clinical investigators should retain either the original or a certified copy of

audit trails.

4. FDA personnel should be able to read audit trails both at the study site and at

any other location where associated electronic study records are maintained.

5. Audit trails should be created incrementally, in chronological order, and in a

manner that does not allow new audit trail information to overwrite existing data

in violation of §11.10(e).

C. Date/Time Stamps

Controls should be in place to ensure that the system's date and time are

correct.

The ability to change the date or time should be limited to authorized personnel

and such personnel should be notified if a system date or time discrepancy is

detected. Changes to date or time should be documented.

Dates and times are to be local to the activity being documented and should

include the year, month, day, hour, and minute. The Agency encourages

establishments to synchronize systems to the date and time provided by trusted

third parties.

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Clinical study computerized systems will likely be used in multi-center trials,

perhaps located in different time zones. Calculation of the local time stamp may

be derived in such cases from a remote server located in a different time zone.

VI. SYSTEM FEATURES

A. Systems used for direct entry of data should include features that will facilitate

the collection of quality data.

Prompts, flags, or other help features within the computerized system should be

used to encourage consistent use of clinical terminology and to alert the user to

data that are out of acceptable range. Features that automatically enter data into

a field when that field is bypassed should not be used.

Electronic patient diaries and e-CRFs should be designed to allow users to make

annotations. Annotations add to data quality by allowing ad hoc information to be

captured. This information may be valuable in the event of an adverse reaction

or unexpected result. The record should clearly indicate who recorded the

annotations and when (date and time).

B. Systems used for direct entry of data should be designed to include features

that will facilitate the inspection and review of data. Data tags (e.g., different

color, different font, flags) should be used to indicate which data have been

changed or deleted, as documented in the audit trail.

C. Retrieval of Data

Recognizing that computer products may be discontinued or supplanted by

newer (possibly incompatible) systems, it is nonetheless vital that sponsors

retain the ability to retrieve and review the data recorded by the older systems.

This may be achieved by maintaining support for the older systems or

transcribing data to the newer systems.

When migrating to newer systems, it is important to generate accurate and

complete copies of study data and collateral information relevant to data

integrity. This information would include, for example, audit trails and

computational methods used to derive the data. Any data retrieval software,

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script, or query logic used for the purpose of manipulating, querying, or

extracting data for report generating purposes should be documented and

maintained for the life of the report. The transcription process needs to be

validated.

D. Reconstruction of Study

FDA expects to be able to reconstruct a study. This applies not only to the data,

but also how the data were obtained or managed. Therefore, all versions of

application software, operating systems, and software development tools

involved in processing of data or records should be available as long as data or

records associated with these versions are required to be retained. Sponsors

may retain these themselves or may contract for the vendors to retain the ability

to run (but not necessarily support) the software. Although FDA expects

sponsors or vendors to retain the ability to run older versions of software, the

agency acknowledges that, in some cases, it will be difficult for sponsors and

vendors to run older computerized systems.

VII. SECURITY

A. Physical Security

In addition to internal safeguards built into the system, external safeguards

should be in place to ensure that access to the computerized system and to the

data is restricted to authorized personnel.

Staff should be thoroughly aware of system security measures and the

importance of limiting access to authorized personnel.

SOPs should be in place for handling and storing the system to prevent

unauthorized access.

B. Logical Security

Access to the data at the clinical site should be restricted and monitored through

the system's software with its required log-on, security procedures, and audit

trail. The data should not be altered, browsed, queried, or reported via external

software applications that do not enter through the protective system software.

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There should be a cumulative record that indicates, for any point in time, the

names of authorized personnel, their titles, and a description of their access

privileges. The record should be in the study documentation accessible at the

site.

If a sponsor supplies computerized systems exclusively for clinical trials, the

systems should remain dedicated to the purpose for which they were intended

and validated.

If a computerized system being used for the clinical study is part of a system

normally used for other purposes, efforts should be made to ensure that the

study software is logically and physically isolated as necessary to preclude

unintended interaction with non-study software. If any of the software programs

are changed the system should be evaluated to determine the effect of the

changes on logical security.

Controls should be in place to prevent, detect, and mitigate effects of computer

viruses on study data and software.

SYSTEM DEPENDABILITY

The sponsor should ensure and document that computerized systems conform

to the sponsor's established requirements for completeness, accuracy, reliability,

and consistent intended performance.

A. Systems documentation should be readily available at the site where clinical

trials are conducted. Such documentation should provide an overall description

of computerized systems and the relationship of hardware, software, and

physical environment.

B. FDA may inspect documentation, possessed by a regulated company, that

demonstrates validation of software. The study sponsor is responsible, if

requested, for making such documentation available at the time of inspection at

the site where software is used. Clinical investigators are not generally

responsible for validation unless they originated or modified software.

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1. For software purchased off-the-shelf, most of the validation should have been

done by the company that wrote the software. The sponsor or contract research

organization should have documentation (either original validation documents or

on-site vendor audit documents) of this design level validation by the vendor,

and should have itself performed functional testing (e.g., by use of test data sets)

and researched known software limitations, problems, and defect corrections.

In the special case of database and spreadsheet software that is (1) purchased

off-the-shelf, (2) designed for and widely used for general purposes, (3)

unmodified, and (4) not being used for direct entry of data, the sponsor or

contract research organization may not have documentation of design level

validation. However, the sponsor or contract research organization should have

itself performed functional testing (e.g., by use of test data sets) and researched

known software limitations, problems, and defect corrections.

2. Documentation important to demonstrate software validation includes:

Written design specification that describes what the software is intended to do

and how it is intended to do it;

A written test plan based on the design specification, including both structural

and functional analysis; and,

Test results and an evaluation of how these results demonstrate that the

predetermined design specification has been met.

C. Change Control

Written procedures should be in place to ensure that changes to the

computerized system such as software upgrades, equipment or component

replacement, or new instrumentation will maintain the integrity of the data or the

integrity of protocols.

The impact of any change to the system should be evaluated and a decision

made regarding the need to revalidate. Revalidation should be performed for

changes that exceed operational limits or design specifications.

All changes to the system should be documented.

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IX. SYSTEM CONTROLS

A. Software Version Control

Measures should be in place to ensure that versions of software used to

generate, collect, maintain, and transmit data are the versions that are stated in

the systems documentation.

B. Contingency Plans

Written procedures should describe contingency plans for continuing the study

by alternate means in the event of failure of the computerized system.

C. Backup and Recovery of Electronic Records

Backup and recovery procedures should be clearly outlined in the SOPs and be

sufficient to protect against data loss. Records should be backed up regularly in

a way that would prevent a catastrophic loss and ensure the quality and integrity

of the data.

Backup records should be stored at a secure location specified in the SOPs.

Storage is typically offsite or in a building separate from the original records.

Backup and recovery logs should be maintained to facilitate an assessment of

the nature and scope of data loss resulting from a system failure.

X. TRAINING OF PERSONNEL

A. Qualifications

Each person who enters or processes data should have the education, training,

and experience or any combination thereof necessary to perform the assigned

functions.

Individuals responsible for monitoring the trial should have education, training,

and experience in the use of the computerized system necessary to adequately

monitor the trial.

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B. Training

Training should be provided to individuals in the specific operations that they are

to perform.

Training should be conducted by qualified individuals on a continuing basis, as

needed, to ensure familiarity with the computerized system and with any

changes to the system during the course of the study.

C. Documentation

Employee education, training, and experience should be documented.

XI. RECORDS INSPECTION

A. FDA may inspect all records that are intended to support submissions to the

Agency, regardless of how they were created or maintained. Therefore, systems

should be able to generate accurate and complete copies of records in both

human readable and electronic form suitable for inspection, review, and copying

by the Agency. Persons should contact the Agency if there is any doubt about

what file formats and media the Agency can read and copy.

B. The sponsor should be able to provide hardware and software as necessary

for FDA personnel to inspect the electronic documents and audit trail at the site

where an FDA inspection is taking place.

XII. CERTIFICATION OF ELECTRONIC SIGNATURES

As required by 21 CFR 11.100(c), persons using electronic signatures to meet

an FDA signature requirement shall, prior to or at the time of such use, certify to

the agency that the electronic signatures in their system, used on or after August

20, 1997, are intended to be the legally binding equivalent of traditional

handwritten signatures.

As set forth in 21 CFR 11.100(c), the certification shall be submitted in paper

form signed with a traditional handwritten signature to the Office of Regional

Operations (HFC-100), 5600 Fishers Lane, Rockville Maryland 20857. The

certification is to be submitted prior to or at the time electronic signatures are

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used. However, a single certification may cover all electronic signatures used by

persons in a given organization. This certification is a legal document created by

persons to acknowledge that their electronic signatures have the same legal

significance as their traditional handwritten signatures. An acceptable

certification may take the following form:

"Pursuant to Section 11.100 of Title 21 of the Code of Federal Regulations, this

is to certify that [name of organization] intends that all electronic signatures

executed by our employees, agents, or representatives, located anywhere in the

world, are the legally binding equivalent of traditional handwritten signatures."

XIII. EXAMPLES OF SOFTWARES OF CLINICAL TRIAL

A. DMSys (SigmaSoft International)

DMSys® is data management software for clinical trials. It is quick to learn and

easy to use. Its design is based on three guiding principles:

GCP and regulatory compliance

User friendliness and efficiency

Affordability

DMSys® is powerful clinical trials software for any pharmaceutical or medical

device company, contract research organization, university department or

governmental/non-governmental organization conducting clinical trials or

performing data management services. DMSys is 21 CFR Part 11 compliant.

SigmaSoft International develops, maintains and supports DMSys. We are

dedicated to providing high quality clinical trials software products

complemented by high quality support, training and service - all at an affordable

cost.

DMSys is a powerful but easy to use data management system for clinical trials.

Our 21 CFR Part 11 compliant software provides all the tools needed to perform

data management, from study setup to data export for statistical analysis.

Complete with full audit trails, performance metrics, rapid data cleaning facilities,

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error management, and query management, the system has many practical

features to streamline the data management process. Our data dictionary

interface allows database structures to be defined and built with zero

programming on the user's part. Data entry screen design is a simple drag-and-

drop process, using a template screen included with the system. Built-in

shortcuts allow study setup files to be copied from a previous study to a new

study, or to a new Form within the same study. Excellent security features allow

the system administrator to specify each user's access privileges, menu item by

menu item, and study by study.

DMSys is extremely flexible. Its rapid study setup facilities make it very cost-

effective in small Phase I trials; while its power and speed mean that it just as

easily handles large post-marketing studies with tens of thousands of patients.

By simplifying the tasks involved in data management, DMSys reduces the

resources required and gives its users a significant competitive edge.

These are some of the features that make DMSys easy to use and a great

clinical trial solution:

A price structure that keeps data management software affordable

System fully validated and compliant with FDA and European regulations

and GCP guidelines

Easy study setup with built-in data checking functions, convenient user

interface and minimum programming

Easy data entry screen setup with drag and drop data entry screen

controls to create your own data entry screens

Integrated shortcuts allow you to copy Forms, data entry screens, logic

checks and all other study structure from Form to Form in the same study

or from one study to another - a major time saver

Flexible data entry options

Single data entry or double data entry (verification)

Data entry in single-form mode (one form for multiple subjects) or

cross-form mode (multiple forms for multiple subjects)

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Interactive or non-interactive verification

Interactive range checks at the point of data entry identifying out of range

values and interactive second data entry identifying inconsistent values

Complete audit trial in compliance with 21 CFR Part 11 including data

entry performance metrics

High-speed platform provides for rapid data cleaning

Error flagging at point of data entry to identify illegible data or other errors

for further follow-up or query

Sophisticated error management function allowing query generation, error

tracking/resolution, and entry of data corrections, including a complete

audit trail, from a single screen

Robust query management capabilities

Allows query generation, tracking and resolution with minimal input

from user

Numerous options for printing queries, including paper or electronic

format, and a customizable Word template that can include your

own logo

Flexible report writing capabilities with over 30 built-in reports

Easy data import from Excel, dBase files and SAS (ASCII) including audit

trail, and allows for second data entry to be performed on imported data

Easy export to Excel, dBase files and SAS (ASCII) including an option for

creating a SAS program that includes input statements and variable labels

Excellent security measures to manage access to software functions and

study data for each individual user

User Validation Package designed to support your validation process

High quality and timely training and support services

Many more features that make DMSys a great tool... let us perform a

demonstration for you.

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B. Open Clinica

OpenClinica is a web-based software platform for managing multi-site clinical

research studies. It facilitates protocol configuration, design of Case Report

Forms (CRFs), electronic data capture, retrieval, and management. OpenClinica

supports HIPAA guidelines, and is designed as a standards-based extensible,

modular and open source platform.

Primary application modules include:

Manage Study: Facilitates configuration and management of studies

(protocols), sites, CRFs, users and study event definitions by study

directors and coordinators. You can define data elements, CRFs, and

protocol events without any custom programming.

Submit Data: Provides a user-friendly web-based interface for subject

enrollment, data submission and validation. For use by clinicians and

research associates involved in patient enrollment and data capture

processes.

Extract Data: Enables data extraction and filtering of datasets for use by

investigators, statisticians, and study directors.

Administer System: Allows overall system oversight, auditing,

configuration, user account management, and reporting by administrators.

Some key features of OpenClinica include:

Organization of clinical research by study protocol and site, each with its

own set of authorized users, subjects, study event definitions, and CRFs.

Support for sharing resources across studies in a secure and transparent

manner.

Dynamic generation of web-based CRFs for electronic data capture via

user-defined clinical parameters and validation logic specified in portable

Excel templates.

Management of longitudinal data for complex and recurring patient visits.

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Data import/export tools for migration of clinical datasets in excel

spreadsheets, local databases and legacy data formats.

Extensive interfaces for data query and retrieval, across subjects, time,

and clinical parameters, with dataset export in common statistical analysis

formats.

Compliance with HIPAA privacy and security guidelines including use of

study-specific user roles and privileges, SSL encryption, de-identification

of Protected Health Information (PHI), and auditing to monitor access and

changes by users.

A robust and scalable technology infrastructure developed using the Java

J2EE framework interoperable with relational databases including

PostgreSQL (open source) and Oracle 10G, to support the needs of the

clinical research enterprise.

C. ClinTriNet

ClinTriNetTM is a web-based application that was created to meet the

needs of investigators in today's research environment. All research activities for

both paper-based and web-based studies, from study proposal to execution to

archiving, are organized, coordinated, and maintained in one system. Particular

users from the customer's organization will be designated as Site

Administrator(s). The Site Administrator has access to all trials conducted at that

site. This person will be responsible for maintaining other users and their

permissions for the site and its trials. Within each site, users are allowed access

to appropriate trials and functions. Within each trial, Trial Administrators maintain

permissions for the trial functions modules, which include communications, data

entry, data cleaning, data retrieval, and administration.

Communications - This module contains a complete messaging system and

project and document management tools. Functions include task and subject

scheduling calendars, and document sharing and archiving.

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Enter Data - Designed to enable the quick completion of on-screen case report

forms for each subject's visit. Data may be double-entered if desired by the

coordinator. Paper-based studies utilize the same interface for CRF

management. These functions eliminate the need for study CRF binders, time-

consuming form management, and subject management paperwork.

Clean Data - A quick, intuitive design allows authorized trial personnel to edit

data and review queries. Queries are based on data format rules, user-created

data validity rules (range and logic checks), double entry verification errors, and

manual notes that can be attached to data at any stage of the trial up to final

database lock.

Retrieve Data - A simple interface allows authorized personnel to download

datasets based upon desired criteria, designed to enable compliance with

HIPAA requirements for de-identified datasets.

Administrate - The Trial Administrator performs routine maintenance of user

and site lists in this module, and has access to complete audit reports of user

actions.

Customized Applications

ClinTriNet was designed to offer investigators the maximum flexibility in

managing trial data while still maintaining an easy-to-use interface. For some

trials, still greater flexibility or special circumstances require modifications to the

core program. In these cases, ClinicalTrialsNet is able to work with investigators

to design program features that best fit their needs. Examples of these are

online randomization, image transfer, specialized data collection forms, and

wireless device compatibility.

XIV. Fundamentals of Clinical Trial Software

1. Clinical trial software ensures clean data. 2. You can manage every step of a study with clinical trial applications.

3. Clinical trial software can generate to-do lists to help you keep your studies on track.

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XV. Benefits of clinical trial software include:

Pharmaceutical, biotechnology, medical device and research

organizations can all benefit from clinical trial software. Clinical trials data

management software assists with all aspects of a trial - from enrollment to study

submission to study archiving. Clinical trial software can be used for small Phase

1 trials or large studies with thousands of participants.

1. Clinical trials data management software can accelerate your study timeline

and control costs without sacrificing the quality of study results.

2. Clinical trial software can ensure compliance with HIPAA, FDA regulatory

guidelines, GCP, 21 CFR Part 11 and even with European regulatory guidelines.

3. With clinical trial applications, you can focus your efforts on your research

rather than on study management.

4. Simplify patient recruitment and scheduling with clinical trial software.

XVI. Tips & Tactics

Helpful advice for making the most of this Guide

Some clinical trial applications allow you to copy study set-ups and forms

from previous trials to a new trial.

Look for security features in your clinical trial applications that allow the

system administrator to set access privileges for each user and for each

study.

Choose clinical trials data management software that integrates with other

software programs, such as Microsoft Excel and other databases.

Opt for clinical trial software that can provide you with the status of all your

ongoing studies on a single screen.

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XVII. REFERENCES

1. FDA, Software Development Activities, 1987.

2. FDA, Guideline for the Monitoring of Clinical Investigations, 1988.

3. FDA, Glossary of Computerized System and Software Development

Terminology, 1995.

4. FDA, [draft] Guidance for Industry: General Principles of Software

Validation, draft 1997.

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