The overall goal of this assignment is to familiarize students with the main categories commonly found in a Data Management Plan (DMP).  Students will review a sponsor’s data management plan and then create a 5 – 6 page DMP for the study site (Good Clinical Trials). The DMP will be based on A Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Clinical Study to Compare the Efficacy and Safety of XYZ Versus Corticosteroid for the Treatment of Lateral Epocondylitis. For this assignment, all data capture is electronic.

Please do not “cut and paste” from the SWP Data Plan example into the template; use your own words.  You will be penalized if you “cut and paste” from someone else’s work. 

Attached to the end of this assignment are:

Data management plan overview for your review

Sponsor’s DMP 

A Template for the Site DMP

Use the following format and sections in your site DMP:

DMP Title

Protocol Title

Overview  (1 – 2 paragraphs) (15 points)

Data Management Staff Roles and Responsibilities (Table Format) (15 points)

Site Policies: related to SOPs and staff training (15 points)

Data Access: access by staff role, security and safety measures; assigning and using passwords, etc.; entry and exit of data management systems (15 points)

Data Entry & Cleaning: prerequisites for data entry (required training & access), granting access, entering data, data security, quality control functions & procedures, and query generation. (15 points)

Monitoring Visits: preparing for monitor visits, protecting data, managing queries, responding to issues. (10 points) 

Database closure checks, quality assurance at closure and database lock, and database unlock. (10 points)

Data Archiving, Record Storage, Retention, and Transfer of final Materials: how and where records will be stored, access to records; length of retention, and how they will be destroyed (10 points)

Adverse & Serious Adverse Events: management of, reconciliation, process and who is responsible for what task related to documenting and reporting (15 points)

GOOD CLINICAL TRIALS – DATA MANAGEMENT PLAN

A Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Clinical Study to Compare the Efficacy and Safety of XYZ Versus Corticosteroid for the Treatment of Lateral Epicondylitis (LE), Protocol Number ASUCNHI/XYZ-LE/16-17/001

Overview

Data Management Staff Roles and Responsibilities

Data Management Staff Roles and Responsibilities

Staff Role

Responsibilities

·

·

·

·

·

·

Site Policies

Data Access

Data Entry & Cleaning

Monitor Visits

Database Closure Checks

Data Archiving Record Storage and Retention

Adverse and Serious Adverse Events Management & Reconciliation

DATAMANAGEMENT PLAN OVERVIEW

A study sponsor should create a Data Management Plan for the study protocol. This plan should be shared with each of the study sites. The management plan is created to ensure that data is collected and managed properly and in compliance with current applicable regulations and guidelines. Each site can modify the data management plan to include site specifics, such as individuals responsible for collecting data, oversight, equipment used, and policies for access.

The FDA provides guidance documents and regulations (21 CFR 11) related to managing data collected in clinical trials. Guidance includes the capture, review, and retention of electronic source data in FDA-regulated clinical investigations. The guidance is the FDAs effort to ensure the reliability, quality, integrity, and traceability of data from electronic source to electronic regulatory submission. (FDA, 2013).

In Guidance for Industry Electronic Source Data in Clinical Investigations (2013) the FDA provides the following definitions related to data management:

· An “electronic record as any combination of text, graphics, data, audio, pictorial, or other information represented in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system.”

· “An eCRF is an example of an electronic record. The eCRF is an auditable electronic record of information that generally is reported to the sponsor on each trial subject, according to a clinical investigation protocol. The eCRF enables clinical investigation data to be systematically captured, reviewed, managed, stored, analyzed, and reported.”

· “Source data includes all information in original records and certified copies of original records of clinical findings, observations, or other activities in a clinical investigation used for reconstructing and evaluating the investigation.”

A Data Management Plan should include the following:

· Data Elements – smallest unit of observation collected on a clinical trial subject. Examples of data elements are weight, height, race, pain severity, etc.

· Data Originators – each data element is associated with an originator, which is the source of that data. Originators might include the study coordinator, the investigator, medical devices such as EKG, consultants, etc.

· eCRFs – the electronic record where data elements are captured.

· Source Documents – the original source of the data element, which can be paper-based or electronic. The source data might be manually entered into the eCRF (for example a radiology report) or electronically transmitted by a medical device (blood pressure monitor).

· Transfer of Source Data Elements into EDC

Paper – manually transferred into the eCRF. The person transcribing the data from the paper source is considered the data originator.

Electronic Transmission – automatic transmission from the device into the eCRF.

· Access – limited access to data by appropriate study staff is important. Access should only be granted to the investigator, study coordinator, data entry staff (if applicable), and data manager (if applicable). Data management must comply with security and privacy measures covered in 21 CFR 11 and HIPAA. The data management plan should include a list of individuals with access to the eCRFs. Individuals with access should have completed appropriate training. Individuals with access should have their own identification codes and passwords. Site policy should include specific instructions to not share access codes and passwords and the consequences of doing so.

· Data Element Identifiers – this is the information that identifies the data originator. These identifiers include:date and time of data entry, originator identification, the subject tied to the data, any changes made and who made the change, when and the reason for change.

· Modifications and Corrections – all data must provide a complete audit trail that allows the reconstruction of the data from initial entry. Only the investigator or qualified clinical study staff should perform modifications to the data.

· Data Review

· Investigator – the investigator is responsible for the conduct of the study and should review and electronically sign-off on eCRFs.

· Monitor – the sponsor is responsible for verifying the data collected in the study is accurate and complete. A clinical research associate (CRA), representative from the sponsor must monitor the study data on a regular basis.

· DSMB – depending on the risk involved in a study, an independent data safety monitoring board (DSMB) may be assigned to review study events to determine that the risk to the subjects is not too great. This board will look for trends in adverse and serious adverse events and provide recommendations on study safety.

· Retention of Records – the investigator is responsible for ensuring that study records are accurate and complete, storing, and maintaining the study records for the required time.

References:

Food and Drug Administration (FDA). (2013) Guidance for Industry Electronic

Source Data in Clinical Investigations

FDA. Code of Federal Regulations, Title 21 part 11: Electronic Records; Electronic Signatures.

Code of Federal Regulations, Title 21 § 50.3: Definitions.

Code of Federal Regulations, Title 21 part 312: Investigational New Drug

Application.

Code of Federal Regulations, Title 21 part 812: Investigational Device Exemptions.

Code of Federal Regulations, Title 45 part 170: Health Information Technology Standards, Implementation Specifications, and Certification Criteria and Certification Programs for Health Information Technology.

Food and Drug Administration, guidance for industry on Computerized Systems Used in Clinical Investigations, available at:

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

.

Food and Drug Administration, ICH guidance for industry E6 Good Clinical Practice: Consolidated Guidance, available at: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.

SWP PHARMACEUTICALS, INC. – DATA MANAGEMENT PLAN

A Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Clinical Study to Compare the Efficacy and Safety of XYZ Versus Corticosteroid for the Treatment of Lateral Epicondylitis (LE), Protocol Number ASUCNHI/XYZ-LE/16-17/001

Overview

21 CFR 312.50 spells out the responsibilities of the study sponsor in the management of clinical trial data and the verification of study data for completeness and accuracy. Thorough review of source data is important to ensure adequate protection of the rights, welfare, and safety of human subjects and the quality and integrity of the clinical investigation data. (FDA, 2013). Sponsor review of source data includes meeting the regulatory requirements for recordkeeping and data verification by use of the ALCOA principle. ALCOA is the acronym for the required components of data. These include:

A = Attributable: originator of the data; who entered the data; audit trail

L = Legible: human readable form, modifications should not obscure original data; audit trail

C = Contemporaneous: time of data entry should be close to when procedure performed; audit trail

O = Original: earliest record, modifications should not obscure original data; audit trail

A = Accurate: correct and complete; valid representation of source data, corrections documented, quality processes/measures used; audit trail.

SWP builds it data management plans around the ALCOA principles with the expectation that chosen study sites comply with ALCOA and the SWP Data Management Plan.

Definitions:

· Data Element – smallest unit of information collected on a clinical trial subject

· Data Originator – original source of the data; may be electronic or human; tied to the data element

· eCRF – electronic Case Report Form

· Source Data – original data (electronic or written)

· EDC – Electronic Data Capture System is provided by the sponsor, data base is created to collected subject data and follows the eCRF format. Data will be either manually entered into the EDC or transferred from a paper form and entered by an individual or automatic transmission from the device into the eCRF.

· Paper – paper forms used to collect subject data

· Electronic – data electronically transferred to the EDC such as EKG results, blood pressure monitors

· Data Element Identifiers – data that identifies the originator including log-in credentials, password, date, time, and subject tied to data.

· Access – Access to study data is limited to study staff who record the data, review the data, and enter the data. For the sponsor, the site monitor generally referred to as a Clinical Research Associate (CRA), statisticians, data entry and data management staff.

· Data Review –

· Data must be reviewed by the study site monitor to verify accuracy and completeness.

· Data reviewed by study coordinator

· Data reviewed by Data entry and data management staff

· Data entered into the EDC must be reviewed and electronically signed off by site investigator

·

Data Modifications & Corrections – to correct data on paper forms, individual correcting data must use black ink and using one-line cross through data, add the correct data in the comment box or next to incorrect data, include reason for change, initial and date the correction. Original data must not be obscured by corrections on paper forms. EDC systems must include functions maintain original data and corrected data, data and time, user, reason for correction/change as required by 21 CFR 11.

· DSMB – Data Safety Monitoring Board. SWP has assigned a DSMB for this study. All adverse events and serious adverse events will be submitted to the DSMB for review. Events to be submitted on a quarterly basis.

· Clinical Research Associate (CRA)/Monitor – Sponsor representative responsible for monitoring the study site to verify subject data and compliance with study protocol and applicable regulations.

· Data Queries – When a monitor notes an inconsistency in data or incorrect data, the monitor will create a query. The individual responsible for the data must review the data query and correct inaccuracies, etc. All queries will be reported and resolved through the EDC system.

Data Points

The following data in Table 1 must be collected on each study subject at the following visits:

Table 1: Schedule of events:

No

Evaluations

Screening

Day 0

Visit 1

Day 1

Visit 2 Week 2

Visit 3 Week 4

Visit 4 Week 12

Visit 5 Week 24

1

Informed Consent

X

2

Inclusion/Exclusion Criteria

X

3

Demographic Data

X

4

Medical History

X

5

Clinical Evaluation

X

X

X

X

X

X

6

Urinary Pregnancy Test
For Female Subjects

X

X

X

X

X

7

Ultrasonography

X

8

Randomization

X

9

Study Drug/Control Drug
(Administered under USG guidance)

X

10

VAS Score

X

X

X

X

X

11

PRTEE Score

X

X

X

X

X

12

ASES Score

X

X

X

X

X

13

Physiotherapy

X

X

X

X

X

14

Adverse Event

X

X

X

X

X

15

Concomitant Medication

X

X

X

X

X

Table 2 lists the individual data points that need to be collected for each of the study events. Refer to Table 1 to identify, which events occur at each visit.

Table 2: Individual Data Points Per Event

Event

Data

Data Point

Informed Consent

Subject ID

Subject Study ID

Date

mm/dd/yyyy

Subject signed & dated

Yes or No

Subject allowed time to review and ask questions

Yes or No

Subject signed prior to initiating study procedures

Yes or No

Subject signed & dated HIPAA

Yes or No

Site designee signed & dated

Yes or No / initials / date / time

Demographic Data

Age

Years

Gender

Male or Female

Race

Hispanic or Latino
Not Hispanic or Latino

Ethnic Group

American Indian or Alaska Native
Asian
Black or African American
Native Hawaiian or Other Pacific Islander
White

Dominant Arm

Right or Left

Height

Feet & Inches

Weight

Pounds

Medical History

Diagnosis of LE

Yes or No

Date of diagnosis

mm/dd/yyyy

Prior treatments for LE

list

Physical Exam

Exam completed by

MD, NP, RN or PA

Name of examiner

First & Last Name

RS

Notes / Abnormality Yes or No; If Yes explain abnormality and any follow-up required; date of follow-up; results

CVS

Notes / Abnormality Yes or No; If Yes explain abnormality and any follow-up required; date of follow-up; results

PA

Notes / Abnormality Yes or No; If Yes explain abnormality and any follow-up required; date of follow-up; results

CNS

Notes / Abnormality Yes or No; If Yes explain abnormality and any follow-up required; date of follow-up; results

Ultrasound

Completed

Yes or No

Results

List

Eligible

Yes or No / Physician Name

Concomitant Medications

Reviewed with subject

Yes or No

Medication

Generic name

Route

Oral, IM, IV, Other (specify)

Dose

Dose amount

Frequency

OD, BD, TID, QID, Other (specify)

Indication

Disease or condition

Start Date

mm/dd/yyyy

End Date

mm/dd/yy or ongoing

Related to AE

Yes or No, AE# if yes

Adverse Events

Reviewed with subject

Yes or No

Event

Name & describe

Start date

mm/dd/yyyy

End Date

mm/dd/yyyy, or ongoing

Severity (determined by PI)

Mild, moderate, severe

Frequency

Single, Intermittent, Continuous

Infusion Related Toxicity

Yes or No

Relationship to IP

Unclassifiable, Unrelated, Unlikely, Possibly, Probably,
Definitely

Action

None,
Medication – started, discontinued,modified,
Hospitalization
Others (specify)

Outcome

Complete Recovery, Recovered w/ sequelae, Ongoing,
Died,
Unknown
Others (specify)

Serious

Yes or No

Reported to the IRB

Yes or No and mm/dd/yyyy

Reported to Sponsor

Yes or No and mm/dd/yyyy

Reported to DSMB

Yes or No and mm/dd/yyyy

Serious Adverse Event

Event

Name & describe

Start date

mm/dd/yyyy

End Date

mm/dd/yyyy, or ongoing

Treatment

Describe

Required ER visit

Yes or No; Name of ER, Name of Health Care Provider(s), Date mm/dd/yyyy

Required hospitalization

Yes or No; Name of Hospital, Name of Health Care Provider(s), Date mm/dd/yyyy

Related to product

Unclassifiable, Unrelated, Unlikely, Possibly, Probably,
Definitely

Reported to the IRB

Yes or No; date-mm/dd/yyyy

Reported to Sponsor

Yes or No; date-mm/dd/yyyy

Reported to DSMB

Yes or No; date-mm/dd/yyyy

Drug Administration

Administered by

Name

Date

mm/dd/yyyy

Drug ID #; Lot #

ID Number; Lot #

Dose

Amount

Anesthesia Used

Yes or No; if yes name of anesthesia and dose

Pregnancy Test

Gender

Male or Female

Performed

Yes or No

If Female & not preformed, reason

Menopause, hysterectomy,

Results

Positive or Negative

Physiotherapy

Conducted

Yes or No

Therapist

Name

Exercises

List exercises

Frequency per week/exercise

1x/2x/3x/4x/5x

Duration

# weeks

VAS

Assessor

Name

Score

0 – 100

PRTEE

Assessor

Name

Score at rest

0 – 10

Score with repeated arm movement

0 – 10

Score carrying a plastic bag of groceries

0 – 10

When pain was least

0 – 10

When pain was worst

0 – 10

Pain – Turn a doorknob or key

0 – 10

Pain – carry grocery bag or briefcase by handle

0 – 10

Pain – Lift a full cup of coffee or glass of milk

0 – 10

Pain – Open a jar

0 – 10

Pain – Pull up pants

0 – 10

Pain – wring our washcloth or towel

0 – 10

Pain – personal activities (dressing, washing)

0 – 10

Pain – House work (cleaning, maintenance)

0 – 10

Pain – work (job or everyday work)

0 – 10

Pain – Recreational or sport activities

0 – 10

ASES – Pain

Assessor

Name

Experience pain in elbow

Yes or No

When at it’s worse

0 – 10

At rest

0 – 10

Lifting heavy object

0 – 10

When doing repeated elbow movements

0 – 10

At night

0 – 10

ASES – Ability to do activities

Assessor

Name

Arm

Right or Left

Button shirt

0 – 3

Manage toileting

0 – 3

Comb hair

0 – 3

Tie shoes

0 – 3

Eat with utensil

0 – 3

Carry a heavy object

0 – 3

Rise from chair pushing with arm

0 – 3

Do heavy household chores

0 – 3

Turn a key

0 – 3

Throw a ball

0 – 3

Do usual work

0 – 3

Do usual sport

0 – 3

ASES – Physician Assessment: Motion

Assessor

Name

Flexion

Right score – degree

Left score – degree

Extension

Right score – degree

Left score – degree

Flexion/Extension Arc

Right score – degree

Left score – degree

Pronation

Right score – degree

Left score – degree

Supination

Right score – degree

Left score – degree

Pronation/Supination Arc

Right score – degree

Left score – degree

ASES – Physician Assessment: Stability

Assessor

Name

Testing affected by pain

Right Arm – Yes or No

Left Arm – Yes or No

Flexion

Right Arm – score

Left Arm – score

Extension

Right Arm – score

Left Arm – score

Pronation

Right Arm – score

Left Arm – score

Supination

Right Arm – score

Left Arm – score

Grip Strength (kg)

Right Arm – score

Left Arm – score

Data Collection

All study data is to be collected and recorded at the time the event/procedure occurs, whether electronically or on paper.

Electronic Data

The following data components will be collected electronically and transferred directly to the electronic data capture (EDC) system:

· Blood pressure measures

· Randomization

· Ultrasound readings

· VAS data/scores

· ASES data/scores

· PRTEE data/scores

Equipment used to record these data will be connected to the EDC system through software provided by SWP Pharmaceuticals. SWP Pharmaceuticals will provide physician assessor with tablet containing assessments and connected to the EDC for automatic transmission of assessment scores.

Paper

The remaining data points will be collected on the paper CRF provided by SWP Pharmaceuticals. Data collected on source documents, such as urine pregnancy will be transferred from source to CRF. The site is responsible for maintaining a subject binder for each subject that includes all CRFs, source documents, notes to file, informed consent, and other essential documents. Subject binders must be stored in a locked area with limited access.

Data Validation

The use of a second staff member to enter data provides a second check of data. The EDC has checks and balances included in the program to verify data is entered correctly. Parameters are built around the data points (such as date limits, age boundaries, proper format of data) to ensure incorrect data options cannot be entered into the system.

Transfer of Data

Data collected on CRFs should be transferred to the EDC on the same day as the subject visit, but no later than two (2) business days after date of subject visit. Data should be entered by a study staff member different from the staff member who collected the data. This will provide a second check for accuracy of data.

Data Access

Only study personnel who have signed a confidentiality agreement and require access to study data to perform their job responsibilities are allowed access to study data. Each person with access must have a verified e-signature on file, and have been assigned an individual and confidential identification and password.

IDs and passwords must not be shared with other staff. Only the assigned individual is to use the password. Passwords must be changed every 180 days, no password can be used more than once. Passwords must be 8 – 16 characters and include at least one uppercase letter, one number and one of the following special characters & % # – _ ( ). The sponsor should review the site policy to verify that it includes specific instructions to not share access codes and passwords.

When a staff member is no longer employed, their ID and password must be removed by the system administrator within 24 hours. When a staff member is terminated their ID and password must be removed immediately.

Investigator Responsibilities

· The site investigator is responsible for ensuring that study data is accurate and complete. This is accomplished by assigning qualified staff to the collect study data and enter data into the EDC.

· The investigator must review subject CRFs that have been entered into the EDC, date and sign that they have been reviewed and are complete.

· Investigator must ensure that data is entered into the EDC within set time.

Ensure that sites AEs and SAEs are reported to the DSMB on a quarterly basis by required deadline.

· The investigator is responsible for storing study records for the time required by the FDA and/or agreed upon in the clinical trial agreement between the site and the sponsor.

Sponsor Responsibilities

· The sponsor will provide the EDC system and provide training to appropriate staff.

· The sponsor will provide the study site with CRFs.

· The sponsor will provide tablets with software installed to transmit electronically captured data to the EDC.

· Sponsor will assign a clinical research associate (CRA) to monitor the site verifying study data and site compliance with protocol, GCPs and applicable regulations.

· The sponsor will provide the DSMB report to each study site within 30 days of the DSMB meeting.

Data Safety and Monitoring Board (DSMB)

SWP Pharmaceuticals has assigned a DSMB for this study who will review adverse and serious adverse events for trends and possible safety issues. The DSMB will meet on a quarterly basis to review safety data from all study sites. Each study site must submit AEs and SAEs to the DSMB fifteen (15) days prior to the scheduled meeting. The DSMB will submit quarterly review reports to the sponsor who will submit copies of report to each study site (within 30 days of the DSMB meeting).

Monitoring

The CRA will monitor the site on a regular basis. Monitoring will consist of reviewing data via the EDC at a central location and by visits at the study site. While on site the monitor will review subject binders to verify data against source documents and check that the data is complete and accurate. When visiting study sites the monitor will also review study records and the conduct of the study for compliance with GCPs, study protocol, and applicable regulations. (Details of monitoring can be found in the Sponsor Monitoring Plan – refer Exercise 1.2: Sample Answer).

When a monitor identifies data that is incorrect or incomplete, he or she will generate a data query via the EDC and assign it to the study coordinator or the staff member who was the originator of the data. The originator of the data is responsible for reviewing and resolving the query within two (2) business days of being notified that the query has been generated in the EDC. Queries are to be resolved via the EDC.

Record Storage & Maintenance

All study documents must be stored in a safe and secure location for a period of two (2) years post approval of the medical product or two years post termination of the study or records are to be stored longer by request of sponsor as covered in the clinical trial agreement (CTA). The site will provide the sponsor with the name and location of storage facility. At the end of the required period the site is responsible for destroying the records in a confidential manner. A note or copy of receipt of destruction of records will be sent by the site to the Sponsor.