1. Lifespan GOOD CLINICAL PRACTICE Record Management GCP May 2005

2. Lifespan What does Good Clinical Practice Mean? Good Clinical Practice (GCP) is an International standard for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials GCPs are consistent with ethical principles put forth in the Declaration of Helsinki If you are in compliance with GCP you ensure: The rights and safety of human subjects are not compromised Appropriately and adequately trained staff manage the study The study is carefully documented The Protocol is strictly adhered to; and, Your clinical trial data are valid, accurate, acceptable and credible May 2005 2

3. Lifespan Where did Good Clinical Practice come from? 1960’s - thalidomide disaster results in a tightening of regulations both in Europe and US. 1977 - the FDA lead the way and introduces a set of proposals for Investigators and Sponsors of clinical trials Between 1986 and 1990 European countries begin to introduce guidelines. With all these different guidelines being introduced the lack of International standards around the world led to problems with data transfer. In April 1996 a meeting was held by the International Committee on Harmonization, ICH (EU, US and Japan). The committee agreed on what are now referred to as the consolidated guidelines that define GCP. May 2005 3

4. Lifespan Guidance for Industry “The Good Clinical Practice: Consolidated Guidance” was issued by DHHS, FDA, CDER, and CBER in April 1996 and became effective in May 1997 Many other countries have since adopted GCP 25 EU Member states issued a directive requiring compliance with GCP by 2004 World Health Organization, WHO, has adopted and requires compliance with GCP May 2005 4

5. Lifespan No, it is not a regulation, however, FDA guidance published May 1997 http://www.fda.gov/oc/gcp/guidance.html states: “The guidance should be followed when generating clinical data that are intended to be submitted to regulatory authorities. The principles may also be applied to other investigations that may have an impact on the safety and well-being of human subjects.” http://www.fda.gov/oc/gcp/guidance.html Compliance with GCP assures that the rights, safety, and well-being of trial subjects are protected and that the clinical trial data are credible. Because the world considers it “best practice” And, last but not least, to be in compliance with your IRB of approval. When the RIH/TMH IRB approves your protocol the approval letter states, “This institution is in compliance with ICH GCP as they correspond to the FDA/DHHS regulations”. The expectation is you will comply with ICH GCP; Why do we Need to Comply with GCP? Is it a regulation? May 2005 5

6. Lifespan “Regulatory Authorities” DHHS Family tree  Department of Health & Human Services Office of the Secretary - (The Assistant Secretary for Health (ASH) serves as the Secretary's primary advisor on matters involving the nation's public health and oversees HHS' U.S. Public Health Service (PHS) for the Secretary).Assistant Secretary for Health  Office of Public Health and Science OHRP Office of Human Research Protection Administration for Children and Families Administration on Aging Agency for Healthcare Research and Quality Agency for Toxic Substances and Disease Registry Centers for Disease Control and Prevention Centers for Medicare and Medicaid Services Food and Drug Administration Health Resources and Services Administration Indian Health Service National Institutes of Health Program Support Center Substance Abuse/Mental Health Services Administration May 2005 6

7. Lifespan Principles of GCP The first basic principle of Good Clinical Practice is the protection of the patient/subject/volunteer. The second basic principle is that the data obtained are correct and reproducible. May 2005 7

8. Lifespan GCP and all it Entails The GCP guidance document is broken down into eight sections. There are certified courses offered in GCP. The course itself is a two day course so you can see how much information the guidance covers. The eight sections are: 1.Glossary2. The Principles of GCP3. The IRB 4. The Investigator5. The Sponsor 6. The Trial & Protocol 7.Investigator’s Brochure8. Essential Documents Section 8 of the guidelines deals with Record Management – Essential documents for the conduct of a Clinical Trial. Incorporated into this section are items from the other sections as you will see. May 2005 8

9. Lifespan Essential Documents for the Conduct of a Clinical Trial 8.1 Essential documents Permit the evaluation of the conduct of a trial and the quality of the data produced. Serve to demonstrate the compliance of the investigator with the standards of GCP and all regulatory requirements. Confirm validity of the trial data May 2005 9

10. Lifespan Before, During and After the Clinical Trial Section 8 of the GCP Guidance document is broken down into groups of documents. The documents required before the trial commences, during the conduct of the trial and after completion or termination of the trial. May 2005 10

11. Lifespan Before the Trial Commences 8.2 Before the trial commences all the documents required for the trial should be compiled into a Regulatory Binder. Investigator’s Brochure, IB, if applicable; IRB Approved Protocol (retain all communication) and CRFs Approved and stamped Informed Consent (retain original to make copies) Advertisements to be used for recruitment Financial agreements, contracts and/or other agreements Regulatory authority authorization/approval (retain all pertinent communication) CV’s of investigators Certification of mandatory human subject protection training for PI and staff Normal lab values and/or tests included in the protocol if applicable Certification, accreditation or validation of labs/facility/procedures/tests Sample of label for device if applicable Instructions for handling product and trial related material if not in IB Shipping records of products for trial Decoding procedures for blinded trials and master randomization list Pre-trial monitoring report and trial initiation monitoring report May 2005 11

12. Lifespan During the Conduct of the Trial 8.3 The following documents should be added as they become required: Updates to Investigator’s Brochure, IB, if applicable Any revisions to Protocol, CRFs, Informed Consent, Ads, etc Correspondence with IRB, updated IC, Continuing Review Notification to Regulatory Authorities re any revisions to above CV of investigators, update every 2-3 years at least, add any new people Updates to normal lab values, procedures, etc Updates to any lab/medical/technical certifications, accreditations, QA or validations Certificates of analysis for any new batches of investigational products Monitoring visit reports. If monitor identifies issues such as deviations or AEs reports should be sent to sponsor and IRB Communications, i.e., AE reports, deviation reports, letters, meeting minutes, notes of telephone calls Signed information consents forms Source documents May 2005 12

13. Lifespan 8.3 Cont’d - The following documents should be added as they become required: Certification of any new staff regarding mandatory Human Subject Protection training as well as HIPAA for Research training Signed, dated and completed case report forms, CRFs. If electronic records perform routine QA on study including CRFs and have PI or study coordinator sign report Documentation of corrections to CRFs. If CRFs are electronic records and changes need to be made archive old record, make changes and save as new. Write up note to file explaining correction and have PI or study coordinator sign and date. Notification of PI to sponsor of AEs, Deviation reports, letters/notes from IRB Notification by sponsor and/or PI to regulatory authorities and IRB of serious AEs and/or any other safety information Notification by sponsor to PI of safety information Interim or annual reports to IRB, sponsor, Regulatory authority Subject Screening log Subject ID code list Subject enrollment log Investigational product accountability at site Staff Signature sheet Record of any retained body fluids/tissue samples if applicable During the Conduct of the Trial May 2005 13

14. Lifespan After Completion or Termination of Trial 8.4 After Completion or termination of the trial, all the documents in Section 8.2 and 8.3 should be in the file together with the following Investigational Product accountability Documentation of investigational product destruction Completed subject ID code list Audit certificate, if required Final trial close-out monitoring report Treatment allocation and decoding documentation Final report by PI/Institution to IRB where required and if applicable, to Regulatory authority Clinical study report May 2005 14