1. Catherine Gregor, MBA, CCRC, CCRP CRC Workshop August 1, 2014
Source Documentation
Catherine Gregor, MBA, CCRC, CCRP
CRC Workshop
August 1, 2014

2. Which of these Study Documents are considered Source documents?
Regulatory Binder
Medical Record
Case Report Form
Participant File
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3. Source Data
The ICH E6 document, section 1.51, defines source data as "All information in original records and certified copies of original records or clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained in source documents (original records or certified copies)."
Source Documents
The ICH E6 document, section 1.52, defines source documents as "Original documents, data and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects' diaries of 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 records kept at the pharmacy, at the laboratories, and at medico-technical departments involved in the clinical trial)."

4. Simple enough right?
But what about Case report forms?

5. When Do Case Report forms become source?
If allowed by the investigational plan (protocol), data may be entered directly onto the case report forms. The case report form would then be considered a source document.
If this case report form is then transmitted to the sponsor, it is necessary for the study site to retain a copy to ensure that the principal investigator can provide access to the source documents to a monitor, auditor, or regulatory agency. Additional information can be found in ICH E6, section

6. Why do we need source Documents?
Data collected in research studies may be useless without adequate and accurate documents
Data that is suspect or cannot be verified may be thrown out
Source documents assist researchers in assuring that each study is compliant with IRB policies and other federal regulatory authorities
If we cant replicate it then it didn’t happen……
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7. What are the regulations and policies that govern research documentation at Vanderbilt?
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8. For any human subjects research conducted at Vanderbilt:
45 CFR 46
Documentation of IRB approval
Documentation of informed consent
Documentation of management of vulnerable populations in accordance with regulations
IRB policies
Documentation of compliance with protocol (inclusion/exclusion, study procedures)
Documentation of adverse event reporting
Documentation of appropriate staff training/qualifications
Documentation of compliance with federal, state and institutional regulations/policies

9. For FDA regulated studies at Vanderbilt 21 CFR 312
For FDA regulated studies at Vanderbilt 21 CFR for drugs and 21 CRF for devices
(a)Disposition of drug. An investigator is required to maintain adequate records of the disposition of the drug, including dates, quantity, and use by subjects. If the investigation is terminated, suspended, discontinued, or completed, the investigator shall return the unused supplies of the drug to the sponsor, or otherwise provide for disposition of the unused supplies of the drug under
(b)Case histories. An investigator is required to prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual administered the investigational drug or employed as a control in the investigation. Case histories include the case report forms and supporting data including, for example, signed and dated consent forms and medical records including, for example, progress notes of the physician, the individual's hospital chart(s), and the nurses' notes. The case history for each individual shall document that informed consent was obtained prior to participation in the study.
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10. “The protocol specified that study drugs were to be prepared by the pharmacist or designee who was trained in the safe handling and administration of a cytotoxic agent. The Infusion Preparation Log for Subject documents that study drugs were prepared on March 24 by an individual identified only by the initials [JKM]. There was no documentation in the study records that [JKM] was the pharmacist or designee, or that [JKM] had been trained in the safe handling and/or administration of a cytotoxic agent.” –FDA Warning Letter   
You failed to personally conduct or supervise the clinical investigation.
You failed to ensure that the investigation was conducted according to the investigational plan.
You failed to protect the rights, safety, and welfare of the subjects under your care.
All of the above.
None of the above.
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11. So where does one begin?

12. Regulatory Binder: Protocol, all versions
Investigators brochures, all versions
Clean case report forms, all versions
Consent forms, all versions
Advertising and recruitment materials, all versions (approval required)
1572, all versions
CVs, current copies for everyone listed on 1572
Verification of staff training
Financial Disclosure/Conflict of interest statement
Lab certifications, reference values, and deliveries
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13. Regulatory Binder (cont)
1. IRB submissions
Original submission
Continuing reviews
Amendments
Adverse Events- local and non- local safety reports
Non-compliance with the protocol (may include items that did not require IRB submission)
2. Keep copies of all submissions, approvals, and correspondence
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14. Regulatory Binder (cont)
Signature/delegation of responsibilities log
Screening and enrollment logs
Drug/device records (may be maintained by the pharmacy if IDS is utilized)
Monitoring Logs
Correspondence
Telephone logs
Notes to file
Miscellaneous
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15. A word about notes to file…
Should not be used exclusively as devices to explain discrepancies
Should not be used exclusively to explain missing or incomplete data
Do Not replace “adequate and accurate case histories” (21 CFR )
Are Increasingly requested by sponsor monitoring staff - not generally temporally associated
Can be Red Flags

16. Notes to file the right way…..
Be generated on a case-by-case basis
Include the subject and protocol it refers to
Be signed and dated by the individual who is writing it
Be legible if handwritten
Explain clearly and specifically the reason for the error/omission/discrepancy or process/policy it aims to address.
Should include any corrective and preventative action or follow-up when applicable.
Be filed with the document, subject file or behind the study binder tab to which it applies

17. Regulatory Binder (cont)
What not to include:
Quality Assurance review findings
Personnel issues
Invoices to sponsor
Contract
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18. Tip for maintaining Study Documents
Maintain papers on a regular basis—don’t let a mole hill turn into a mountain.
Set time once a week to make sure your binders are in order.
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19. What is a Participant File?
A file containing the study documents pertaining to an individual participant in your study
The participant file should contain all information needed to reconstruct a participant’s activities on study
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20. What should be in Participant files?
Original signed consent form
Case report form
Questionnaires
Records of materials and drugs given to participant, drugs returned
Medical history
Record of study visits
Physician notes
Memos to file
Adverse Events
Diaries
Communications ( s and phone calls)

21. Source Document Tips Do: Don’t: No white-out No pencil No back-dating
Have signature lines for portions of your CRF that are used as source documentation
Date and initial all notations
Use blue or black pen
Correct errors with a single strike through, date and initial
Include the subject ID on all pages in record
Use subject ID instead of names to protect patient privacy
Keep files in locked cabinet/room
Don’t:
No white-out
No pencil
No back-dating
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22. Case report forms are used in order to collect data in a standardize way and ensure that all data elements are captured. Data are recorded on the forms for each subject in the study and then entered/transfered into a database.
Case Report Forms
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23. Case Report Forms Generally Includes: Inclusion/Exclusion criteria
Demographic information
Medical history
Medications
Lab tests
Clinical endpoints and outcomes
Adverse events
Study summary and PI evaluation
**If you are developing your own CRF, be sure to pilot it before beginning enrollment. Poorly designed CRFs result in poorly collected data.
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24. Study Closeout-how long should you maintain study records?
Drug or device studies:
Two years AFTER the drug approval was granted or denied OR the length of time stated in the contract with the sponsor – whichever is greater
HIPAA requires 6 years after study closure
Behavioral and Social Science studies:
Three years AFTER the study has been closed with the IRB
Archive, Archive, Archive
ASK BEFORE DESTROYING ANYTHING
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25. Key Points
Remember, organizing your paperwork can be as important as dispensing the right drug. Researchers protect human subjects by having paperwork in order.
Don’t have multiple collection “dumps”
Remember your patients confidentiality—use names as minimally as possible. Keep files in locked cabinet/room.
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26. Questions?