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