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Project Title: Development of a comprehensive Clinical Trials Management System (CTMS) for a pharmaceutical research organization
Background
Clinical trials are done to see if a new drug or device is safe and effective for people to use. Clinical trials are also done for other reasons such as comparing existing treatments to determine the better one. The current, approved treatments are called the "standard treatments." Sometimes clinical trials are used to study different ways to use the standard treatments so they will be more effective, easier to use, and/or decrease side effects. Sometimes, studies are done to identify the best treatment among different population, such as children, for whom the treatment was not tested previously.
For most trials, researchers, doctors, and other health professionals administer the clinical trials according to strict rules set by the Food and Drug Administration (FDA). FDA sets the rules to make sure that people who agree to be in studies (also called Subjects) are treated as safely as possible.
Trials are done in four phases: Phase I tests a new drug or treatment in a small group; Phase II expands the study to a larger group of people; Phase III expands the study to an even larger group of people; and Phase IV takes place after the drug or treatment has been licensed and marketed.
A Clinical Trial Management System, also known as CTMS, is used by the bio-technology and pharmaceutical companies to manage large amounts of data involved in the operation of a clinical trial. In early phases of clinical trial, where the number of patients were small in amount, companies used in-house or home-grown programs to handle their research. As the number of patients increased day-by day, the researchers are replacing their systems with rich-featured and more stable products from vendors. Some of the improved features in the system are -
Budgeting, Dashboards, Adverse Events Reporting and better compatibility with other good management information Systems.
CTMS has the following modules - improved features like Study(is the kind of research or the name given for research),Site(is the place where research is held),Subject(is the patient who comes voluntarily,eg:if the researchers have found a medicine for cancer,they have to test the medicine on the human body,and the patient who comes voluntarily are called Subject),Sponsor (is who sponsors for a Subject).Clinical Trial has to keep track of few modules like,
a)Study Management: Study module maintains the primary details of the clinical trial such as the type of disease, the medicine being tested, company sponsoring the study, whether the Study is interventional or observational and the geographic locations where the study will be held.
b)Subject Screening And Enrollment: Subject is the patient who voluntarily assigns himself for a Study. Testing in humans is permitted only if that person volunteers for participation and understands the risks and benefits of taking part in a study. Subject Screening is to get the details of Subject and his Clinical State (the condition of patient).
c) Visit Scheduling And Load Balancing: This module keeps track of the visits of Subject to a site, fixing of appointments, and scheduling subsequent visits. The module ensures that the patient visits are optimally scheduled so that there are an almost equal number of patients coming in on various days.

d) Managing Case Report Forms: The Case Report Form is the tool used by the sponsor of the clinical trial to collect data from each participating site. All data on each patient participating in a clinical trial are held and/or documented in the CRF, including adverse events. This keeps track of the details of drugs given to the subject, test results etc..,
e) Financial Budget: Budget is the total amount of money allocated towards internal and external costs of conducting the Study.
f)Adverse Events: An adverse event (AE) is any adverse change in health or "side-effect" that occurs in a person who participates in a clinical trial while the patient is receiving the treatment (study medication, application of the study device, etc.) or within a pre-specified period of time after their treatment has been completed.
g) Management Dashboards: Dashboard lets you view the actual progress and milestones of every study and site in a graphical representation ”alongside projections”so you™re the first to know if a study or site is falling behind. Intuitive access to such meaningful data allows proactive controls throughout study performance.
h) System Administration

STUDY MANAGEMENT:
Study describes the drug or the device that is being tested. Details of the study are published in a document called Protocol after it is approved by the government. This document describes the objective(s), design, methodology, statistical considerations, and organisation of the clinical trial and usually also gives the background and rationale of the trial.
The purpose of this module is to capture and manage important protocol-related data. This includes items like the precise protocol title, number and study phase, the IND or IDE number and date, and the therapeutic area, indication, and method of treatment.

The primary tasks in this module include “ adding a study (or protocol), editing, viewing and deleting study information. Each study has a unique list of authorized users, so they can only access studies for which they have appropriate permissions.
Following is the study-oriented tasks .
a) Adding a Study:

¢ General Study details include the following attributes:

ATTRIBUTES Description
Study #
Sponsor name Company sponsoring the study
Phase Trials are done in four phases: Phase I tests a new drug or treatment in a small group; Phase II expands the study to a larger group of people; Phase III expands the study to an even larger group of people; and Phase IV takes place after the drug or treatment has been licensed and marketed.
Study Status The current status of study. Active / Declined / Completed / Terminated / On Hold / Enrollment closed
Brief title Short note about the Study
Protocol title
Study Regions These are different regions where the trials will be conducted. Typically a region corresponds to a continent.
Study Design a)Interventional
b)Observational

¢ Study Info provides the details about the interventional and observational.
Interventional: Interventional includes the following attributes:

ATTRIBUTES DESCRIPTION
Interventional Primary purpose Purpose of intervention
masking
allocation
no.of arms various kinds of test for the study

¢ Arm1(describes the kind of test for the study..):

ATTRIBUTES DESCRIPTION
Target Subject Population
Arm label Defines the name of the arm
Arm type
Arm Description precise writing about the arm1

¢ Arm2 (describes the second kind of test for the study..)

ATTRIBUTES DESCRIPTION
Target Subject Population
Arm label Defines the name of the arm
Arm type
Arm Description precise writing about the arm2
Therapeutic Area
Clinical State (the state in which the study is).
Study Article
Study classification
Target Subject Count
IRB
IRB contact
FWA
Special Population Yes/no type
Ind/Ide #
IND/IDE approval date
IRB approval date

Observational: Observational includes the following attributes:

ATTRIBUTES DESCRIPTION
Primary Strategy for Subject Identification & follow-up
Time Prospective
no.of groups various kinds of observational for the study

¢ Group 1( various kinds of observational for the study):
Group1 includes the following attributes:

ATTRIBUTES DESCRIPTION
Target Subject Population
Interactive type
Interaction name
Interaction Description precise writing about the interaction


¢ Group 2( various kinds of observational for the study):
Group2 includes the following attributes:
Same as like group1and also includes the following:

ATTRIBUTES DESCRIPTION
Bio-specimen
sampling method
primary out come measure
time frame
safety issue yes/no
Secondary outsource measure
time frame
safety issue yes/no
masking
allocation
Therapeutic Area
Clinical State the state in which the study is
Study Article
Study classification
Target Subject Count
IRB
IRB contact
FWA #
Special Population yes/no
Ind/Ide #
IND/IDE approval date
IRB approval date

¢ Study Criteria contains the following attributes:

ATTRIBUTES DESCRIPTION
Target no.of sites Total no.of sites or place where the Study is held.
Target no.of Subjects No.of Subjects or the participants in the Study
duration of study
lead time
treatment period
Follow up period
Enrollment Start & End Date

¢ SPONSOR contains the following attributes:

ATTRIBUTES DESCRIPTION
Sponsor project manager
sponsor legal
contact#
email
contract manager
medical monitor
contact#
email

¢ STUDY REGION contains the following attributes: In this activity, user will associate a study with one or more regions. The attributes involved will be

ATTRIBUTES DESCRIPTION
study region
study status region
comments

These regions will be pre-defined in a master list. User will also have to select the status from a list of pre-defined status codes.
¢ STUDY COUNTRY contains the following attributes:

ATTRIBUTES DESCRIPTION
Study country
Study country status
no.of sites
no.of subjects No.of subjects in the country
IEC/IRB name
address Address of the site
contact no. Contact number of the site
email Email id of the site
comments

¢ STUDY SITE contains the following attributes:

ATTRIBUTES DESCRIPTION
Country Name of the country
site Name of the Site in the respective country
investigator name and type
site address Address of the site
status
city
state
postal code
targeted subjects
planned enrollment start&end date

¢ STUDY VENDORS contains the following attributes:

ATTRIBUTES DESCRIPTION
Vendor #
Vendor name
Vendor type.

¢ STUDY ASSOCIATION (Clinical Research Organization(CRO)-Staff) contains the following attributes:

ATTRIBUTES DESCRIPTION
name
role
site#/name
lead yes/no

¢ STUDY ASSOCIATION(INVESTIGATOR) contains the following attributes:

ATTRIBUTES DESCRIPTION
Study#
Sponsor Protocol #
Site#
Investigator type
Investigator name


b) Editing a Study:
1) General Study Details and the Study Info cannot be edited.

2) Study criteria, Study sponsor, Study region, Study country, Study site, Study vendors, Study Association of CRO, Study Association of Investigator, can be edited.

c) Deleting a Study:
1) General Study Details and the Study Info cannot be deactivated.
2) Study criteria, Study sponsor, Study region, Study country, Study site, Study vendors, Study Association of CRO, Study Association of Investigator, data can be deactivated or deleted.


SUBJECT SCREENING AND ENROLLMENT:
Subject is the person who voluntarily comes for the research to be done on him / her. For example, a medicine has been found by the researchers. So they want a subject, so that they can test the medicine on the Subject. For a subject to be registered inside ctms, there are few tasks like adding the subject details, editing, and deleting the one on whom is the research conducted.
a) Adding the Subject details:
Adding the subject, requires the following tasks to be done:
¢ SUBJECT CREATION involves adding General details of the subject and adding the contact details.
GENERAL SUBJECT CREATION DETAILS:

ATTRIBUTES DESCRIPTION
SALUTATION Mr/Mrs/Ms
FIRST NAME First name of the Subject
MIDDLE NAME Middle name of the Subject
LAST NAME Last name of the Subject
SUBJECT # Subject id
GENDER Male/Female
RACE
ADDRESS LINE 1 Address line 1
LINE 2 Address line2
CITY City to which the Subject belongs
STATE State to which the Subject belongs
ZIP/POSTAL
DATE OF BIRTH
AGE
SUBJECT STATUS
REFERRAL TYPE
REFERRAL NAME

¢ CONTACT INFO OF SUBJECT:

ATTRIBUTES DESCRIPTION
WORK PHONE # Work phone number of the Subject
HOME PHONE
MOBILE NO.
FAX NO.
EMAIL ADDRESS
RESPONSIBLE PARTY
ADDRESS LINE 1
ADDRESS LINE 2
CONTACT NO
ZIP/POSTAL CODE
STATE
COMMENTS

¢ SUBJECT STUDY ASSOCIATION links the subject to the particular study in which he/she will be participating.

ATTRIBUTES DESCRIPTION
STUDY #
SITE #/SITE NAME
STUDY START DATE Study start day for the Subject
STUDY END DATE Study End day for the Subject
SCREENING #
SCREENED DATE
RANDOMIZATION #
RANDOMIZATION DATE

¢ CLINICAL STATES datastore maintains the illnesses, disease and
other conditions of the subject.

ATTRIBUTES DESCRIPTION
CLINICAL STATES
ACTIVE
START DATE
END DATE
COMMENTS

¢ SUBJECT STUDY ARTICLE/CONCOMITANT MEDICATIONS

ATTRIBUTES DESCRIPTION
STUDY ARTICLE
ACTIVE YES/NO
START DATE
END DATE
Comments

¢ CONCURRENT MEDICATIONS captures details of other medications that the subject is taking in addition to the medication under study.

ATTRIBUTES DESCRIPTION
MEDICATIONS
ACTIVE YES/NO
START DATE
END DATE
Comments

b) Editing the Subject Details:
All the data can be edited.
If any particular data is found to be incomplete or inaccurate, a note can be added so that the supervisor can review it and make appropriate correction.
c) Deleting the Subject Details:
Subject can be deleted only if it does not have any Case Report Forms and scheduled visits. Otherwise, it can be de-activated. De-activation means that the physical record will exist in the database but its status is set to Inactive. For inactive subjects, case report forms can not be added. Also, new visits can not be scheduled.

VISIT SCHEDULING AND LOAD BALANCING:
Scheduling determines the Subject visit to the respective site. This module enables adding, editing and deleting of the Subject visit details.
a)Adding details of Subject Visit:

ATTRIBUTES DESCRIPTION
S.NO
SUBJECT #
SUBJECT NAME
NEXT DUE VISIT
APPOINTMENT DATE
APPOINTEMNT SESSION

In adding of Subject visit, Subject name should be from the Subject master table. Appointment date should be checked from the master table wherein, the appointment dates are to be pre-defined in a calendar type. System should pro-actively suggest dates where the number of appointments are low so that the load on the doctors is optimized. If the appointment dates are full in master table, then the system should be able to automatically intimate that no appointments can be made in the respective dates. Appointment session has to be filled based on the number of subjects, and the recording of time has to be allowed.
b) Editing of Subject Visit: Editing of Subject Visit or Rescheduling of visit should be allowed based on the master table details.

c) Deleting of Subject Visit:

Deleting of Subject Visit, should be allowed based on the master table details. Past appointments can not be deleted.

MANAGING CASE REPORT FORMS(CRF):
These are Electronic questionnaires specifically used in clinical trial research. The Case Report Form is the tool used by the sponsor of the clinical Trial to collect data from each participating site. All data on each patient participating in a clinical trial are held and/or documented in the CRF, including adverse events.

a)Adding of CRF details:

¢ ASSENT FORM1 has the following attributes:

ATTRIBUTES DESCRIPTION
Research Title
IRB Protocol #
Is this a research study
What you need to know about research studies
Why are you being asked to participate in this research study
What is this research study about
What will happen during this study
Will the study hurt
What else should I know about the study

¢ ASSENT FORM2 has the following attributes:

ATTRIBUTES DESCRIPTION
What are the good things that might happen
What if I don't want to be in this study
Who should I ask if I have any questions
Do I have to be in the Study
Comments
Your Signature
Age
Date
Signature of Witness
Name of Witness
Date
Signature of Person Obtaining Consent
Name of Person Obtaining Consent
Date

¢ SCREENING has the following attributes:

ATTRIBUTES DESCRIPTION
Date of Visit
Effective Date
Inclusion Criteria
Exclusion Criteria
Eligibility

¢ DRUG ADMINISTRATION has the following attributes:

ATTRIBUTES DESCRIPTION
S.NO.
START DATE
TIME
COURSE #
DRUG
LOT #
DOSE LEVEL & UNITS
ACTUAL DOSE & UNITS
SCHEDULE
ROUTE
DURATION
UNITS

b) Editing of CRF details:
Assent form1, Assent form2, Screening andDrug Administration forms can be edited.
c) Deleting of CRF details: Assent form1, Assent form2, Screening, Drug Administration can be deactivated or deleted after appropriate approval.

FINANCIAL BUDGETING & ACCOUNTING:

Financial budget in CTMS describes the total amount of funding available for internal and external costs for a study at a site. Many budgets like - Start up budget, Fixed Study budget, and Per Subject Budget are maintained. Budget Summary provides the total cost for the subject.
a)Adding of budget and accounting :
¢ NEW BUDGET has the following attributes:

ATTRIBUTES DESCRIPTION
Sponsor Protocol #
Study #
Site #
Budget Status
Budget Name
Budget Description
Cost Based Cost Overhead %
Charged Based Cost Overhead %

¢ ADMIN DOCUMENTATION has the following attributes:

ATTRIBUTES DESCRIPTION
S.NO
ACTIVITY
SUB ACTIVITY
COST PER UNIT a)INTERNAL
b)EXTERNAL
NO. OF UNITS
UNITS QTY/TIME IN MINUTES/DAY
TOTAL COST
a)INTERNAL
b)EXTERNAL
COMMENTS

¢ STARTUP BUDGET has the following attributes:

ATTRIBUTES DESCRIPTION
S.NO
ACTIVITY
COST PER UNIT a)INTERNAL
b)EXTERNAL
NO. OF UNITS
UNITS QTY/TIME IN MINUTES/DAY
TOTAL COST
a)INTERNAL
b)EXTERNAL
COMMENTS

¢ FIXED STUDY BUDGET has the following attributes:

ATTRIBUTES DESCRIPTION
S.NO
ACTIVITY
COST PER UNIT a)INTERNAL
b)EXTERNAL
NO. OF UNITS
UNITS QTY/TIME IN MINUTES/DAY
TOTAL COST
a)INTERNAL
b)EXTERNAL
COMMENTS

¢ PER SUBJECT BUDGET has the following attributes:

i)VISIT PLAN has the following attributes:
ATTRIBUTES DESCRIPTION
Visit #
Visit Name
Days to Next Visit
Appointment Range
Status
Unexpected Visit
Days to Monitor
Effort to Monitor (in Hrs)
CRF Pages to Complete

¢ ACTIVITY has the following attributes:

ATTRIBUTES DESCRIPTION
Visit #
Activity Name
Provider Type
Provider Name
Unexpected Visit
Internal Cost
External Cost
Type of Units
Comments

¢ BUDGET SUMMARY has the following atttributes:

ATTRIBUTES DESCRIPTION
Start Up Cost
a)INTERNAL
b)EXTERNAL
Fixed Cost
a)INTERNAL
b)EXTERNAL
Subject Cost Per Subject
a)INTERNAL
b)EXTERNAL
Subject Cost for all Subjects
a)INTERNAL
b)EXTERNAL
Variable Cost
a)INTERNAL
b)EXTERNAL
Expenses Cost
a)INTERNAL
b)EXTERNAL
Total
a)INTERNAL
b)EXTERNAL

Editing Budget details: New budget, per subject budget, fixed Study Budget and Admin documentation can be edited.
c) Deleting Budget Details: New budget, per subject budget, fixed Study Budget, Admin documentation can be deleted after appropriate approval. Budget summary can not be deleted as it is derived information.

ADVERSE EVENTS REPORTING:
When a medicine is given to the Subject, if the subject suffers other side effects that are not related to this treatment, they are called as adverse events. This information is vital for a clinical trial and it needs to be reported to authorities.
a)Adding adverse events details:
Adding of adverse events is divided into three types:
a)Adverse event1
b)Adverse event2
c)Adverse event3

¢ ADVERSE EVENT1 has the following attributes:

ATTRIBUTES DESCRIPTION
SPONSOR PROTOCOL #
SUBJECT NUMBER
INVESTIGATOR TYPE
INVESTIGATOR NAME
STUDY PHASE
SPONSOR NAME
SITE#/SITE NAME
STUDY TITLE
SUBJECT NAME
CRC NAME

¢ ADVERSE EVENT2 has the following attributes:

ATTRIBUTES DESCRIPTION
RANDOMIZATION#
START DATE OF ADVERSE EVENT
RESOLVED DATE
INVESTIGATOR /CRC REPORTED DATE
ADVERSE EVENT DESCRIPTION
TOXICITY TYPE CODE
GRADE/SEVERITY
SERIOUS ADVERSE EVENT
SERIOUS EVENT TYPE
DOSE
FREQUENCY
ROUTE
THERAPY DAYS
DRUG LOT NO.
EXPIRATION DATE

¢ ADVERSE EVENT3 has the following attributes:

ATTRIBUTES DESCRIPTION
RELATION
EXPECT
STATUS OF AE WITH REGARD TO SUBJECT
ACTION
THERAPY
CONCOMMITANT MEDICATIONS
OUTCOME
DOSE LIMITING TOXICITY
Does AE require modifications to the Informed Consent
Does AE require modifications to the Investigative Brochure
Date AE Reported to Sponsor
IRB Report Date
IRB Report Type
AERS Report Submitted
AERS Report Date
Comments
ADEERS Report Submitted
ADEERS Report Date
Comments

b)Editing the Adverse Event Details:
Adverse event1, Adverse event2 and Adverse event3 can be edited.
c)Deleting the Adverse Event Details:
Adverse event1, Adverse event2, Adverse event3 can be deactivated.

MANAGEMENT DASHBOARDS:

Dashboard provides a graphical representation of total number of Studies, Sites, Subjects enrolled, visits completed, pending etc. The information displayed includes the following -
a) the number and percentage of studies by status.
b) the target number of enrollments for each study vs actual number enrolled (total across sites)
c) the target number of subjects at each site vs actual number enrolled (for a specific study)
d) the target number of subjects for each study vs actual number enrolled (at a particular site)
e) the number of subjects who completed a visit vs number of subjects pending for all visits by study by site.

SYSTEM ADMINISTRATION
This module covers the following functionality “
a) Security “ Access rights for various users
b) Master table maintenance
c) Common functions such as logging and archiving