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SWPPHARMACEUTICALSDMP.docx

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.