Good Clinical Practice (GCP) and Monitoring Practices Office of Human Subjects Research Institutional Review Board (IRB) Open House Good Clinical Practice (GCP) and Monitoring Practices Frederick W. Luthardt, DBE, MA Manager, OHSR Compliance Monitoring Program Suzanna Roettger, MA Senior Compliance Monitoring Specialist Bryan Moore, MA, CCRP

Good Clinical Practice (GCP) Supplements FDA/HHS regulations for the conduct of human subjects research: i.e., Guidelines that compliment Federal Law. Outlines the expectations for investigators in Human Subjects Research GCP is found in the International Conference for Harmonization (ICH) E6: Good clinical practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects.” “Compliance with this standard provides public assurance that the rights, safety, and well-being of trial subjects are protected, consistent with the principles that have their origin in the Declaration of Helsinki” “and that the clinical trial data are credible.”

The Principles of ICH GCP 2.1 Clinical trials should be conducted in accordance with the ethical principles. 2.2 Before a trial is initiated, foreseeable risks should be weighed against the anticipated benefit. 2.3 The rights, safety, and well-being of the trial subjects are the most important considerations 2.4 The available non-clinical and clinical information on an investigational product should support the proposed clinical trial. 2.5 Clinical trials should be scientifically sound, and described in a clear, detailed protocol. 2.6 A trial should be conducted according to the protocol having received prior IRB approval. 2.7 The Subject’s medical care should always be the responsibility of a qualified physician.

The Principles of GCP continued… 2.8 All research personnel in a trial should be qualified by education, training, and experience. 2.9 Informed consent should be obtained from every subject prior to clinical trial participation. 2.10 All clinical trial information should be recorded, handled, and stored to promote accurate reporting, interpretation and verification. 2.11 The confidentiality of records should be protected. 2.12 Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). 2.13 Systems with procedures that assure the quality of every aspect of the trial should be implemented

Monitoring and Auditing: What are they? The Compliance Monitoring Program Distinct from what the IRB does. Can occur at 2 levels: Internal (conducted by the Principal Investigator) External (conducted by the institution, like the OHSR CMP and/or the sponsor) Monitoring and auditing are different Involve different levels of scrutiny and for different purposes Assessing Do PIs do what they said they would do (following the protocol) Are PIs (and study team members) in compliance (following the rules)

General Activities of the Monitoring Program Review a “snap shot” of the every day operations of selected studies Generate an evaluative summary of a study’s progress Offer corrective action/best practices suggestions to the Principal Investigator and study team members Provide this information to the IRBs, Assistant Dean for Human Research Protection, and the Vice Dean for Clinical Investigation.

Activities of the Monitoring Program Assessment of attention to human subject safety requirements by observing and evaluating: Adherence to IRB approved consent procedures Proper screening and enrollment of eligible subjects Use of a Data Safety and Monitoring Plan (DSMP) Appropriate and prompt reporting of unanticipated problems & protocol changes Documentation of protocol procedures in the subject record & data collection forms

What do we see out there? Missing regulatory information Consent form signature and date problems Incomplete or overlooked study procedures that were not documented (“protocol deviations”) Deficient eligibility assessments Deficiencies in reporting Unanticipated Problems or Untoward occurrences

Questions we get… Does our program “shut down” studies? How are studies selected for routine/High Risk monitoring? What does the IRB do with our reports? My study is already being monitored by the study’s sponsor, will you still do a monitoring visit? Do you have any tools or resources to help investigators? Can we invite OSHR monitors to look at our study? What do I do if FDA is going to audit my study?

Thank You! Questions? Contact Information: Fred Luthardt: fluthar1@jhmi.edu Suzanna Roettger: sroettg1@jhmi.edu Bryan Moore: bmoore31@jhmi.edu Feel free to drop by!