Research Coordination Guidance

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Research Coordination Guidance

• The Committees on Human Research
• Serving
• University of Vermont Fletcher Allen Health
  Care

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• The following material is intended as guidance on
  how to achieve good standards and/or best
  practices in the conduct of research with human
  subjects.
• It is meant to be an adjunct to the basic human
  subjects protection training information provided
  in the required on-line tutorial.
• The goal is to provide practical advice and tips
  on how to implement good practices to achieve
  high quality research results while ensuring the
  protection of research participants.

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Good Clinical Practice (GCP)

• Developed for clinical research, GCP is an
  international ethical and scientific quality
  standard applied to human subject research that
  impacts
• Study design
• Conduct
• Record management
• Data collection and reporting

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Good Clinical Practice

• Compliance with GCP standards provides public
  assurance that the rights, safety and well-being
  of human subjects are protected and that the
  study data are credible.

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Applying GCP Standards to ALL Types of Research

• The principles established by GCP are typically
  applied to biomedical research, but it is
  recommended that they also be applied to other
  studies which have an impact on the safety and
  well-being of human subjects. This includes
  research in the behavioral sciences.

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GCP Objectives

• Basic Principles of GCP
• Compliance with Protocol
• IRB Reporting Requirements
• The Process of Informed Consent
• Record Data Management
• PI Research Member Responsibilities

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Principles of GCP

• The rights, safety, and well-being of the
  research subjects are the most important
  considerations and should prevail over interests
  of science and society (E6 2.3)

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Principles of GCP

• Each individual involved in study conduct should
  be qualified by education, training, and
  experience to perform his or her respective tasks
  (E6 2.8)
• The principal investigator should be qualified by
  education, training, and experience to assume
  responsibility for the proper conduct of the
  study, should meet all the qualifications
  specified by the applicable regulatory
  requirements, and should provide evidence of such
  qualifications through up-to-date CV and/or other
  relevant documentation requested by the sponsor,
  IRB, and/or the regulatory authorities (E6
  4.1.1)

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Principles of GCP

• Informed consent should be obtained from every
  subject prior to study participation (E6 2.9)
• All study information should be recorded,
  handled, and stored in a way that allows its
  accurate reporting, interpretation and
  verification (E6 2.10)

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Principles of GCP

• The confidentiality of records that could
  identify subjects should be protected, respecting
  the privacy and confidentiality rules in
  accordance with the applicable regulatory
  requirements (E6 2.11)
• Systems with procedures that assure the quality
  of every aspect of the study should be
  implemented (E6 2.13)

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Compliance with the IRB-approved Protocol

• A study should be conducted in compliance with
  the protocol that has received prior IRB approval
  (E6 2.6 4.5.1)
• If you conduct research that deviates from the
  IRB approved protocol then you are in
  noncompliance
• Serious and continuing noncompliance is
  reportable to federal regulatory authorities,
  sponsors and institutional officials

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IRB Reporting Requirements

• Protocol Amendments
• Protocol Deviations
• Unanticipated Problems Involving Risks to
  Subjects or Others

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Protocol Amendments

• Changes to the study must be submitted for IRB
  review (E6 4.4.3 4.10.2)
• Examples of study changes
• Study procedures
• Adding, revising or eliminating measures
• Surveys, questionnaires, data collection forms,
  etc.
• Recruitment materials
• Study termination, suspensions, and final closure
  (E.6 4.12 4.13)
• Only implement protocol changes after you receive
  notice of IRB approval

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Protocol Deviations

• Report promptly to the Committee deviations from
  the IRB-approved protocol that increase or may
  increase risk to subjects or others (E6 4.5.2
  4.5.3)
• Report all other protocol deviations at time of
  continuing review
• Provide an action plan to avoid recurrence
• Amend protocol
• Create departmental or study specific SOPs

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Unanticipated Problems Involving Risks to
Subjects or Others (UAPs)

• Report local events that meet all 3 of the
  criteria below
• Unexpected
• Related to the study AND
• Pose harm or a potential for harm to subjects or
  others
• (E6 4.11)

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Different Types of Potential UAPs

• Physical (e.g. adverse events)
• Emotional or psychological harm (e.g., stress and
  anxiety)
• Social harm (e.g., stigma)
• Financial harm (e.g., loss of employment or
  insurability)
• Legal harm (e.g., criminal or civil liability)
• Invasion of privacy or embarrassment due to
  breaches of confidentiality

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The Process of Informed Consent

• Create an Informed Consent Process
• Informed consent is not a single event or just a
  form to be signed
• Need a detailed plan that describes the informed
  consent process
• Ongoing Consent
• Ongoing discussions regarding the study is
  imperative in assessing a subjects willingness
  to continue study participation

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Obtaining Legally Effective Informed Consent

• Before informed consent may be obtained, the
  investigator, or a person designated by the
  investigator, should provide the subject ample
  time and opportunity to inquire about details of
  the study and to decide whether or not to
  participate (E6 4.8.7)
• All questions about the study should be answered
  to the satisfaction of the subject (E6 4.8.7)

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Obtaining Legally Effective Informed Consent

• Prior to a subject's participation in the study,
  the informed consent form should be signed and
  dated by the subject and by the person who
  conducted the informed consent discussion (E6
  4.8.8)
• Prior to participation in the study, the subject
  should receive a copy of the signed and dated
  informed consent form (E6 4.8.11)

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Sharing New Information

• The informed consent form should be revised
  whenever important new information becomes
  available that may be relevant to the subject's
  consent.
• The subject should be informed in a timely manner
  if new information becomes available that may be
  relevant to the subject's willingness to continue
  participation in the trial.
• Revised informed consent form(s) or consent
  addendums must receive IRB approval in advance of
  use.
• The communication of this information should be
  documented.
• (E.6 4.8.2)

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Record Data Management

• PI must ensure that research records are
• Accurate
• Complete
• Legible
• Available for audits
• (E6 4.9.1 4.9.7)

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Data Collection Instruments (DCI)

• Review protocol thoroughly to create useful DCIs
  to collect imperative data points
• Forms/instruments must include
• Data collection dates
• Subject identifiers

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Source Documents

• Source documents are original documents, data,
  and records (i.e. medical records, chart notes,
  lab reports, memos, subject diaries and
  checklists, x-rays, pharmacy dispensation logs,
  etc.)
• Data reported on DCIs should be consistent with
  source documents otherwise discrepancies should
  be explained and documented (E6 4.9.2)

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Correcting Data

• Any changes or correction to data should be
• Dated
• Initialed
• Explained (if necessary)
• Do not obscure original data
• Example
• 010 MMH 6/21/07
• Subject 001 was seen today, 06/01/2007, for
  a follow-up study visit. She reported no
  significant changes since her last visit. She
  had questions about when she would receive study
  payments. PI to follow-up with subject regarding
  her questions.
• (E6 4.9.3)

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Maintaining Essential Documents

• Essential Documents are those documents which
  individually and collectively permit evaluation
  of the conduct of a study and the quality of the
  data produced.
• These documents serve to demonstrate the
  compliance of the investigator with the standards
  of GCP and with all applicable regulatory
  requirements.
• (E6 8.1)

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Maintaining Essential Documents

• Filing essential documents in a timely manner can
  greatly assist in the successful management of a
  study.
• These documents are also the ones which are
  usually audited by the sponsor and inspected by
  the regulatory authorities as part of the process
  to confirm the validity of the study conduct and
  the integrity of data collected.

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Maintaining Essential Documents

• Most Essential Documents are maintained in either
  the
• Regulatory Binder
• Subject Files

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Regulatory Binder

• Copy of IRB application and all corresponding
  documents submitted and approved by the IRB
• Copies of correspondence to and from the IRB
  including initial IRB approval letter, copies of
  consent form(s), assent form(s), parental
  permission form(s) with IRB approval stamp
• Continuing review forms and approvals
• Amendment forms and approvals
• Copies of any advertisement(s) and IRB approval
• Copy of related grant application

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Regulatory Binder

• Screening Logs
• Enrollment Logs
• Randomization Logs
• Refer to the Regulatory Binder Set-up and
  Maintenance available on IRBs Education Website
  for more detailed guidance on the contents of a
  typical regulatory binder.

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Subject Files

• Signed consent forms, assent forms, or parental
  permission forms
• Consent forms may be kept in a secure and
  separate location from the data, however there
  must be a key to link consent documents to real
  data
• Source documents (e.g. blood test results or
  x-rays)
• Data Collection Instruments (i.e. forms, surveys)
• Proof that all inclusion/exclusion criteria were
  assessed
• Follow-up Assessments
• Exit Procedures

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Principal Investigator Must Ensure

• All persons assisting with the study are
  adequately informed about the protocol, the
  investigational products, and their study-related
  duties and functions (E6 4.2.4).
• Prompt reporting to the IRB of any changes in
  research activity including any changes to the
  protocol, and/or consent form(s) and
  unanticipated problems
• No change in approved research may be initiated
  without the IRBs approval except under
  conditions where it is necessary to eliminate
  apparent immediate hazards to human participants

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Members of the Research Team Must

• Adhere rigorously to the IRB approved protocol
• Inform PI of all unanticipated problems
• Ensure the adequacy of the informed consent
  process
• Take measures necessary to ensure adequate
  protection for subjects

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Useful Tools

• The following tools are available on the IRBs
  Education Website
• Regulatory Binder Set-up and Maintenance
• Human Subjects Protection Program Investigator
  Self-Assessment

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References

• Good Clinical Practice Consolidated Guideline
  ICH Topic E6

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Where to go for more Information?We are here to
help!

• The Research Protections Office is located off
  campus at
• 245 South Park, Suite 900, Colchester and
• our phone number is 656-5040.
• Website http//www.uvm.edu/rpo/