Good Clinical Practice

1. Good Clinical Practice Jennifer McCormick MA, CRC Karla Lichter RN CCRC

2. Good Clinical Practice • Good clinical practice is an international ethical and scientific quality standard for designing, conducting, recording and reporting clinical trials. • FDA issued guidance in 1994 & 1995. • In 1996 the guidelines were endorsed by the ICH (International Conference on Harmonization)

3. Good Clinical Practice GCPs are divided up into the following eight sections: • Glossary of terms • Principles of ICH GCP • IRB responsibility/guidelines • Investigator responsibility/guidelines • Sponsor responsibility/guidelines • Clinical protocol & amendments • Investigator Brochure • Essential Documents

4. Good Clinical Practice Objectives: Review the 13 Principles of GCP Identify relevant GCP’s for investigators and sites Demonstrate competency of GCP(section 4)

5. Good Clinical Practice Principles of GCP • Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and consistent with GCP and applicable regulatory requirements. • Before a trial is initiated, foreseeable risks should be weighed against the anticipated benefit.

6. Good Clinical Practice Principles of GCP • Rights, safety & well being of trial subjects must prevail over interests of science & society • Non clinical & Clinical information on an investigational product should be adequate to support the clinical trial • Clinical trials must be scientifically sound & described in a detailed protocol

7. Good Clinical Practice Principals of GCP • A trial should be conducted in compliance with the protocol & received IRB approval • Medical decisions & care of subjects should be responsibility of qualified physician • Each individual involved in conducting a trial should be qualified by education, training & experience to perform respective tasks

8. Good Clinical Practice Principals of GCP • Freely given informed consent should be obtained prior to trial participation • All trial information should be recorded, handled & stored in a way that allows accurate reporting, interpretation & verification • Confidentiality of records (de-identify)

9. Good Clinical Practice Principals of GCP • Investigational Product should be manufactured, handled & stored in accordance with Good Manufacturing Practice & the protocol • Systems with procedures that assure the quality of every aspect of the trial should be implemented

10. Good Clinical Practice Investigator Qualifications • Investigator(s) should be qualified by education, training & experience, should meet all the qualifications specified by applicable regulatory requirements & should provide evidence of qualifications through an up dated CV • Investigator should be familiar with the investigational product as described in the protocol/Investigator Brochure

11. Good Clinical Practice Investigator Qualifications • Investigator should be aware of and comply with GCP & regulatory requirements • Investigator/site should permit auditing/monitoring by sponsor & applicable regulatory authorities • Investigator should maintain a list of appropriately qualified persons whom tasks have been delegated.

12. Good Clinical Practice Adequate Resources • Investigator should demonstrate potential for recruiting the required number of subjects within the recruitment period • Investigator should have sufficient time to conduct & complete the trial • Investigator should have adequate number of qualified staff & adequate facilities • Investigator should ensure all persons assisting with the trail are informed of the protocol, investigational product & their trial related duties

13. Good Clinical Practice Medical Care of Trial Subjects • A qualified physician who is an investigator or sub-investigator should be responsible for all trial related medical decisions • Ensuring & following a subject’s participation in a trial the investigator should ensure adequate medical care is provided for AE’s, significant lab values related tot the trial. The investigator should inform a subject when medical care is needed for intercurrent illness

14. Good Clinical Practice Medical Care of Trial Subjects • It is recommended the investigator inform the subject’s PCP about the subject’s participation & if the subject agrees to the primary physician being informed • Although a subject is not required to give a reason for withdrawing from a trial, the investigator should make a reasonable effort to obtain the reason for withdrawal

15. Good Clinical Practice Communication with IRB • Before initiating a trial, the investigator should have written & dated approval from the IRB for the protocol, ICF, ICF updates, subject recruitment material or other written information provided to the subject • Investigator should provide the IRB with the IB and any IB updates • During the trial the investigator should provide the IRB all documents subject to its review.

16. Good Clinical Practice Compliance with the Protocol • Investigator should conduct the trial in compliance with the protocol, sponsor, regulatory authorities and IRB. The investigator & sponsor should sign the protocol or other contract to confirm agreement • Investigator should not deviate from the protocol without agreement by the sponsor & IRB except when necessary to eliminate immediate hazards to a subject or if the changes are logistic/administrative ( i.e. change in phone number or monitor)

17. Good Clinical Practice Compliance with the Protocol • Investigator or a person designated by the investigator should documents & explain any deviation • Investigator may deviate from the protocol to eliminate an immediate hazard to subject without prior IRB approvable. As soon as possible the deviation & reason for the deviation should be reported to the IRB, sponsor & if applicable regulatory authorities

18. Good Clinical Practice Investigational Product (IP) • Responsibility for the IP accountability at the site rests with the investigator/institution • Where allowed this duty can be assigned to a designated pharmacist or appropriate individual who is under the supervision of the investigator/institution • Records should be maintained on product delivery to the site, inventory at the site, use by the subject and return of unused IP from the subject and return to the sponsor

19. Good Clinical Practice Investigational Product (IP) • Records should include dates, quantities, batch/serial numbers, expiration date & unique code numbers assigned to the IP & subjects. Documentation should specify subjects were provided the doses specified by the protocol & reconcile all IP received from the sponsor • IP should be stored as specified by the sponsor & in accordance with applicable regulatory requirements

20. Good Clinical Practice Investigational Product (IP) • Investigator should ensure the IP is used on accordance with the approved protocol • Investigator or designated person should explain the correct use of the IP to each subject & check at intervals each subject is following the instructions

21. Good Clinical Practice Randomization and Un-blinding • Investigator should follow the randomization & un-blinding procedures in accordance to the protocol. • If un-blinding occurs the investigator should promptly document the reason for un-blinding & notify the sponsor

22. Good Clinical Practice Informed Consent • In documenting and obtaining consent the Investigator must comply with applicable regulatory requirements, GCP, Declaration of Helsinki & IRB • ICF should be revised when important new information is available and approved by the IRB prior to use. The subject or subject’s legal representative should be informed in a timely manner & the communication of this information should be documented

23. Good Clinical Practice Informed Consent • Investigator/staff should not unduly influence or coerce the subject to participate or continue to participate • Language should not appear to release the investigator, institution, sponsor or agents from liability for negligence • Investigator or designated person should fully inform the subject or legal representative all aspects of the trial

24. Good Clinical Practice Informed consent • Language written or oral should be nontechnical as practical & be understandable • Ample time for review, decision to participate & inquire about details of the trial should be provided to the subject or legal representative • Prior to subject participation the ICF should be signed & dated by the subject/legal representative and person obtaining consent

25. Good Clinical Practice Informed Consent • If a subject/legal representative is unable to read an impartial witness should be present during the entire consent discussion. After the discussion and the subject/legal representative has orally consented & if capable signed & dated the ICF the witness should personally sign & date the ICF. The witness signature attests the information was accurately explained & understood by the subject/legal representative

26. Good Clinical Practice Informed Consent • The informed consent should contain all required elements • Prior to participation the subject/legal representative should receive a copy of the current signed/dated ICF and any updated ICF • Assent should be obtained from minors or subjects with impaired cognitive function. If capable the subject should sign/date the ICF

27. Good Clinical Practice Informed Consent • Nontherapeutic trials may be conducted in subject with consent of a legal representative provided the following is fulfilled: • Objectives of the trial cannot be met by means of a trial in subjects who can give informed consent • Foreseeable risks are low • Negative impact on the subject’s well-being is minimized & low • Trial is not prohibited by law • IRB is sought on inclusion of such subject & written approval covers this aspect Such trials should be conducted in subjects having the disease or condition for which the IP is intended. Subjects should be closely monitored & withdrawn if unduly distressed

28. Good Clinical Practice Informed consent • A nontherapeutic trial (no clinical benefit to the subject) should be conducted in subjects who personally give consent & sign/date the ICF • In an emergency situation when prior consent is not possible the consent of the legal representative if present should be obtained. If the legal representative is not available enrollment of the subject should require measures described in the protocol with documented approval by the IRB. The subject’s legal representative should be notified as soon as possible

29. Good Clinical Practice Records and Reports • Investigator should ensure the accuracy, completeness, legibility & timeliness of data reported • Data on the CRF which are derived from source documents should be consistent with the source or discrepancies explained • Any change or correction should be initialed, dated & explained (if necessary) & should not obscure the original entry.

30. Good Clinical Practice Records and Reports • Investigator should maintain the trial documents as specified in Essential Documents for the Conduct of a Clinical Trial & applicable regulations • Essential documents should be retained 2 yrs after the last approval of a marketing application in an ICH region or longer if required by the sponsor or regulatory requirements

31. Good Clinical Practice Records and Reporting • Financial aspects of the trial should be documented in an agreement between the sponsor and investigator • Upon requests of the monitor, auditor, IRB or Regulatory authority the investigator should make available for direct access to all requested trial related records. • Investigator should submit written summaries of the trial status to the IRB annually or more often if requested

32. Good Clinical Practice Records and Reports • Investigator should promptly provide written reports to the sponsor, IRB, if applicable regulatory authority/institution any changes that significantly affects the conduct of the trial and/or increases risk to the subject • All SAE’s should be reported within the time periods defined by the sponsor and other applicable regulatory authorities • AE’s and/or lab abnormalities identified as critical in the protocol to safety evaluations should be reported to the sponsor within time periods defined

33. Good Clinical Practice Records and Reporting • For reported deaths, the investigator should supply the sponsor, IRB with any additional requested information(autopsy reports) • If a trial is prematurely suspended for any reason the investigator should ensure appropriate therapy & FU for the subjects & inform the regulatory authorities • If investigator terminates a trial without prior agreement of the sponsor, the investigator should inform and provide detailed written explanation to the sponsor, IRB and regulatory authorities

34. Good Clinical Practice Records and Reporting • If the sponsor terminates a trial the investigator should promptly inform (if required) the institution and IRB. The investigator should provide a written explanation of the termination • If the IRB terminates the trial the investigator should inform the institution (if required) and the sponsor & provide the sponsor an explanation

35. Good Clinical Practice • Upon completion of the trial, the investigator should (if applicable) notify the institution, notify the sponsor & IRB and provide a summary of the trial’s outcome.

36. Good Clinical Practice Questions