1. Research Documentation Betty Wilson, CIP, MS Senior Compliance Manager MU IRB Lori Wilcox, EdD Director of Academic Compliance, Corporate Compliance

2. Overview  Research design and purpose  Importance of validity and reliability  Multiple stakeholders, purposes and processes  Source Documentation  How to make corrections or appropriately document unexpected or adverse events or errors

3. Anatomy of Clinical Trial Research  Regardless of source (internal or sponsor) primary components include:  Research question – the “So What”  Significance – provides the context  Design – complex and multiple types  Study population – specific target  Variables – what is being measured  Data management and analysis  Maintaining validity and reliability for each component is crucial

4. Documentation regarding the study population  Essential that protocol defines the specific inclusion and exclusion criteria  Population estimate needs to be as accurate as possible  If documentation validating each subject’s inclusion and exclusion criteria is not complete AND accurate, the entire research study is jeopardized

5. Documentation regarding treatment/intervention  Also essential that the protocol provides clear and detailed explanation of the treatment/intervention for all arms or phases of the trial  Failure to adhere to the precision provided in the protocol for each study participant will invalidate the data and jeopardize the research

6. Why is monitoring clinical trials important?  To ensure the intervention is not unexpectedly harmful  If unexpectedly effective, not to delay next steps  Discontinue if no possibility of addressing research question  To ensure study sites are providing ethical interventions while maintaining the reliability and validity of the research

7. Who cares about your documentation?  Principal Investigator (PI)  Patient(s)  IRB  Corporate Compliance  Sponsor  FDA  Other regulatory bodies/organizations  Insurance companies/third party payors

8. What is Source Documentation Original documents, certified records of original data, records of clinical findings, observations, or other activities necessary for the reconstruction and evaluation of the study Examples: hospital records, clinical and office charts, laboratory results, subjects’ diaries, evaluation checklists, pharmacy dispensing records, x-rays, MRI, etc.

9. Source Documentation 21 CFR 312.62, 511.1(b)(7)(ii) and 812.140, state the clinical investigator must retain records required to be maintained under part 312, § 511.1(b), and part 812, for a period of time specified in these regulations. This requirement applies to the retention of the original source document, or a copy of the source document.

10. Case Report Forms The document provided by the sponsor or created by the PI for the collection of specific data to evaluate the study including adverse events. Data may be entered directly onto the case report forms. The case report form would then be considered a source document. This form should be signed and dated by the person who has collected the information to verify the information is accurate. Case report forms should NOT contain the subject’s name or SSN.

11. Electronic Data Capture as Source  Secure log in  Must be secure (HIPAA compliant for PHI)  Be able to indicate who completed the task (verification by the actual responsible person)  Can have built in checks/flags  Can serve as source for certain data points  SOP required indicating responsibilities for creating, modifying, maintaining and transmitting  Verify with sponsor if considered source

12. The Goal: Concise, complete, accurate, and consistent data that covers all data/information needed for the study Consider: What data points are needed for the final analysis What needs to be covered for compliance with the regulations

13. What needs to be documented? If it is not documented, it is not done  Consent  Inclusion/exclusion criteria  Randomization  All Data points for each study visit  Unanticipated events :  Unexpected (not in supporting documents/ different frequency or severity )  Potentially related (previous medical history)  Potential for harm

14. Data Points  Check protocol  Table of events  Specific instructions for processing or preforming tasks  Check consent  Check any specific manuals for processing  Space or place for interpretation (i.e. lab values for clinical significance)

15. Considerations  Use chronological order of visit  Place in order that is easy to follow  Consider page numbers  Place subject ID on the top of each page  Consider the version number (match to protocol)  Update as protocol is updated  Check boxes may require supporting documentation  Do not use abbreviations unless defined or standard

16. Filling out Source Docs  Who can do what (credentialing)  Complete in a timely manner (same day/visit)  Fill out headers  No Blank Pages!  Indicate if not done and why  Record data even if it is not the expected result  Must be readable – Do Not recopy for neatness  Late entries must be indicated as such  Source Documents must NOT be DISCARDED

17. Corrections  Do Not use white out  Do Not scribble over errors erase  Always use a pen (not pencil)  Line through error  Initial and date  Write in correction  Initial and date any late additions  Addendum to EMR

18. Notes to file When to use  Indicate information is stored elsewhere  Clarifies across the study When NOT to use  To replace source documentation  To explain numerous deviations Alternatives: Source documentation Correspondence with the sponsor/monitor