Karen Barnwell, Auditor

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Common Audit Findings

• Karen Barnwell, Auditor
• Office of Research Compliance

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Regulations Considered During an Audit

• 21 CFR 50 Protection of Human Subjects
• 21 CFR 56 Institutional Review Boards
• 21 CFR 312 Investigational New Drug Application
• 45 CFR 46 Protection of Human Subjects
• ICH E6 Good Clinical Practice Consolidated
  Guidance
• IRB Standard Operating Policies Procedures
• IRB Investigators Handbook
• http//www.fda.gov
• Code of Federal Regulations or Guidance Documents
• under Reference Room
• http//www.uams.edu/irb/IRB.asp

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UAMS Common Findings

• Informed Consent
• Protocol Deviations/Violations
• Study Records
• IRB

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Common FDA Audit Findings

• Inadequate Informed Consent
• Failure to Adhere to Protocol
• Inadequate/Incorrect Records
• Failure to Notify IRB of Changes
• Use of Unapproved Concomitant Meds
• Problems with Record Availability
• Failure to Obtain IRB Approval
• Failure to Obtain Informed Consent
• (These are from inspections through 4/5/04)

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INFORMED CONSENT
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Informed Consent Findings

• No PI Signature/Stamped Signature
• Dates Missing/Incomplete/Different
• Times Incomplete Too Much Time Between
  Signatures
• Missing Informed Consent Forms
• Informed Consent Process Documentation

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Informed Consent Process

• ..No investigator may involve a human being as a
  subject in research unless the investigator has
  obtained the legally effective informed consent
  of the subject or the subjects legally
  authorized representative. An investigator shall
  seek such consent only under circumstances that
  provide the prospective subject or the
  representative sufficient opportunity to consider
  whether or not to participate and that minimize
  the possibility of coercion or undue influence.
  The information that is given to the subject or
  the representative shall be in language
  understandable to the subject or the
  representative
• 45 CFR 46.116

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Steps in Informed Consent Process

• Starts with an interview
• Is an exchange of essential information about the
  research
• Allows an opportunity for participant to ask
  questions and have them answered
• Is evidenced by the signing of informed consent
  document
• Is documented in record
• Requires giving a copy of the Informed Consent
  form to the participant
• Continues at each interaction by providing the
  participant new information as it develops

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Who Does the IC Interview?

• Who can conduct the Interview to obtain Informed
  Consent?
• The PI
• A sub-investigator
• A study staff person, listed with the IRB, whom
  the investigator has documented is fully
  conversant with the study and is able to answer
  participants questions

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The Informed Consent Document

• Use the current, IRB approved version

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Informed Consent Document

• The ICD should
• Contain all required elements
• Describe the study in language the person can
  understand
• Be signed, dated and timed by
• Subject or Legally Authorized Representative
  (LAR)
• Witness
• Investigator
• Person obtaining the consent
• The person signing as the witness cannot be the
  same as the person obtaining consent or the
  investigator

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PROTOCOL DEVIATIONS/VIOLATIONS
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21 CFR 312.60General responsibilities of
investigators.

• An investigator is responsible for ensuring that
  an investigation is conducted according to the
  signed investigator statement, the
  investigational plan, and applicable regulations

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Protocol Findings

• Inclusion/Exclusion Criteria
• Very Detailed Protocol Blood Samples, Blood
  Tests, Phone Calls, Sites of Procedures
• Dates/Times of Protocol Required Procedures
• Randomization Procedure

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Research?Medical Practice
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Patients vs. Participants

• When a person volunteers for a research trial,
  he/she has become a participant.
• Participants may not be receiving standard of
  care as a patient. The risks may be higher
• Documentation for participants is more extensive
  than regular patient documentation

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STUDY RECORDS
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Study Record Findings

• Source Data Not Available/Not Signed or Dated
• Data Changes Made Incorrectly
• Signature Logs
• Study Staff Responsibility Chart
• CVs Outdated/Missing
• Licenses Expired/Missing
• HSP/HIPAA Training Missing

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I.R.B.
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IRB Findings

• CR Expired
• Protocol Deviations/Violations Not Reported
• SAEs/AEs Not Reported or Reported Late
• Use of Unapproved Material
• Approved Accrual Goal Exceeded
• Study Personnel Not Up-To-Date/Incomplete
• Incomplete IRB Files Missing IRB
  Correspondence/Other

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IRB Investigators Handbook

• Chapter 8 - Research Record-Keeping and Reporting
  
• ARIA Information
• Record-Keeping Responsibilities Of The Principal
  Investigator (PI)
• Investigators Responsibilities For Test Article
  Accountability
• Subject Information Regarding Investigational
  Drugs Or Devices
• Investigator IRB Reporting Responsibilities
• Change in Principal Investigator
• Communicating With Subjects
• Reporting Responsibilities Of The Principal
  Investigator To The IRB
• Adverse Event Reporting
• How To Report A Death Or Serious Adverse Event
• Reporting Protocol Deviations
• Reporting Protocol Violations
• Reporting Notification Of Pending Audits Or
  Inquiries
• Reporting to Appropriate Federal Oversight
  Bodies, Institutional Officials and Research
  Sponsors
• Changing Study Protocol/Modifications to
  Previously Approved Research

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An ounce of prevention is worth a pound of cure!
OR
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Slay your dragons before they slay you!