Responsible Conduct of Research: Research RegulationsRachel Sheppard, MBA, CCRC, CCRA
Goals
Know the resources the University of Louisville offers to help you stay in compliance.
Gain a basic understanding of the regulations governing clinical research.
Learn to ask permission and not forgiveness.
Investigator Responsibilities
Gain written IRB approval
Keep a research file and case report for each subject
Conduct study according to written protocol
Be knowledgeable about all interventions
Records of use of drug/device (accountability)
Personally supervise the investigation
Ensure proper billing as it relates to research
Investigator Responsibilities (cont.)
Ensure subjects understand what is investigational about the protocol
Ensure all personnel are qualified/trained
Reporting any event that affects research to IRB
Ensure that IRB is compliant with regulations
Maintain approval of study
Record retention
Training required
HIPAA fundamentals and security
CITI Biomedical Course
CITI GCP Training (recommended)
Annual SFI disclosure
Blood-borne pathogen Training
Basic Safety Laboratory Training (BSL 1/2)
Additional training
Case Reports
Defined as medical information collected and presented on three or fewer patients to highlight an interesting treatment, presentation, or outcome
Authorization if identifiers are present (18 HIPAA)
Done without prior “research” intent
Does not meet the university definition of research
IRB review is required
Observational research
Documents required Complete Waiver IRB application/approval Protocol Data collection forms Billing Compliance Table (BCT) Hospital approval (if applicable) Retrospective or prospective research If prospective, many other forms…similar to
interventional research
Interventional research
Documents required Partial Waiver Informed Consent Form Protocol Research Authorization IRB application IBC application (if applicable) Data collection forms Billing Compliance Table (BCT) Hospital approval (if applicable) If sponsored, many other forms…
Documents for Screening and Enrollment
Informed Consent Form (ICF)
Research Authorization (RA)
Partial Waiver
Complete Waiver
What are these documents and their purpose?
Rule of 50
Documentation of Consenting process
Consent Documentation in Records
Name of person obtaining consent
Date of consent
A thorough discussion/explanation of the study was provided and with whom, i.e. subject family members, LAR.
Potential subject and/or LAR was allowed time to ask questions
All questions were answered
Potential subject verbalized understanding of the information provided
Subject or LAR agreed to participate in the study
Subject or LAR signed the ICF and Research Authorization
Study procedures were not performed prior to consent
Goals/Responsibilities: Informed Consent Process
Give subject information about the research
Make sure there is adequate time
Determine ability to give informed consent Cognitive status Ability to read Free of undue influence by others Primary language spoken
Answer all questions
Determine understanding of subject
Obtain voluntary consent; free of coercion
Continue to inform subject
Legally Authorized Representative
The individual that has the legal right to consent for the treatment/research
Kentucky State Statute
When to use Protocol allow IRB/local law
Call IRB for Guidance
Document, document, document!!!
Re-consenting Reasons Protocol changes
New safety information
New alternative treatments
Pediatric patient reaches 18
Original consent process not done properly
Potential for capacity to consent may fluctuate
Substantial period since consent elapsed
Other changes mandated by IRB or sponsor
Data collection guidelines
Always write with ink; not pencil Record all data requested or indicate ND or NA Only make justifiable changes by doing the following:
One line through entry Record new value Initial and date
Do not record data outside fields or write on the back Record data on forms; not on napkins or scrubs Try to collect specific data; not open-ended fill in the
blank Be consistent
Protocol Violations
What is a protocol violation?
Reported based on major and minor
Major – Affects subject rights, safety, wellbeing and/or the completeness, accuracy and reliability of data
Reportable to IRB FDA, OHRP or other agency arrives/notifies for audit
Termination or suspension of research
SAEs/AEs
Protocol violations
New findings
Changes in personnel/procedures
DSMB reports
Breach of confidentiality of data
Incorrect labeling/dosing of test article
Reportable to IRB Discrepancy in accountability of test article
Unauthorized use of PHI
Subject complaints
Incarceration of a subject
Unexpected pregnancy of a subject or partner
Suicide attempt of subject while in research
Death of healthy volunteer within 30 days of participation
Injury of study personnel
Any problem that is unanticipated, related and affects the safety and welfare of subjects
Billing Compliance Example
Examples of contingent procedure billing
Schedule of Events important tool
What is purpose of HIPAA
Using Health Information without Authorization
Treatment, Payment and Operations (TPO)
De-Identified Data
Limited data set with Data use agreement
Activities preparatory to research
Deceased Individuals
Waiver of authorization
Waiver of Authorization
45 CFR 164.512(i)
No more than minimal risk Plan to protect identifiers Destroy at earliest opportunity PHI will not be reused or disclosed except by law
The research cannot be “practicably” conducted without waiver
The research cannot be “practicably” conducted without PHI
Texting and Research
Very easy to violate the HIPAA regulations!
Privacy Office can advise on the use of Tigertext app
Common IRB findings
Incorrect versions of stamped documents signed
Unapproved versions of documents signed
Lack of documentation of consent process
PI signature after time limit
Failure of PI to sign/date documentation
Incorrect/omitted signatures/dates on documents
LAR not well documented (identity, reason)
More common findings
Lapse in IRB approval
Unreported SAEs/protocol violations
Assents signed by parents and not child
No re-consent of 18 year old
Personnel added to study without IRB approval
Missing source documentation
Enrollment numbers not accurate with IRB reports
Lack of policies and procedures for research conduct
Governing Authorities for Research
Federal Regulatory Agencies
DHHS overarching agency for the following: FDA (device and drug research) NIH (peer reviewed research) OHRP (oversees both FDA and NIH research) CMS (approval of billing for research procedures)
Code of Federal Regulations Title 21, Food and Drugs Title 45, Public Welfare
FDA has adopted ICH Guideline E6 Good Clinical Practice (recommendation)
Office of Civil Rights (enforces HIPAA regulations)
Research Structure at UofL and HSC
OCRSS assists in the approval process
Resources HSPPO Website http://louisville.edu/research/humansubjects
U of L Investigator Guide Generic SOPs ICF process documentation form Auditors available for educational sessions 24-hr Hotline: 1-877-852-1167
Clinical Trial Networks website https://www.ctnbestpractices.org
FDA website http://fda.gov
Association of Clinical Research Professionals http://acrpnet.org
OCRSS Glossary of Terms (handout)
Common Initialisms in Research