Good Clinical Practice

Transcription

1 Dublin Academic Medical Centre Good Clinical Practice Patrick Murray, MD, FASN, FRCPI Professor, University College Dublin, Mater Misericordiae University Hospital, Dublin, Ireland CR Clinic Researc Cent

2 Good Clinical Practice (GCP) GCP is an international ethical & scientific quality standard for.. Designing, Conducting, Recording, Reporting trials that involve the participation of human subjects

3 ICH-GCP: Lecture Outline ICH-GCP History ICH-GCP Principles Ethics Committee Responsibilities (see S. O N) Investigator Responsibilities Patient Safety

4 ICH-GCP History 1964 Declaration of Helsinki 1974 Belmont report 1977 USA GCP (FDA) 1987 France GCP; Germany- conduct of clinical trials; Ireland Clinical Trials Act (1990) 1989 Nordic GCP 1991 European GCP 1996 ICH (International Conference on Harmonisation) GCP: EU, Nordic countries, Japan, USA, Australia, Canada, WHO 2004 EU Clinical Trials Directive Trial Registration- Irish Medicines Board: IMB Medicines Listingwww.imb.ie/EN/Medicines/HumanMedicines/HumanMedicinesListing.aspx

5 Declaration of Helsinki Gold standard ethical guidance document for all research conducted in human subjects First version published in 1964 by the World Medical Association Use is mandatory if you wish to publish in ICJME (International Committee of Medical Journal Editors) publications 2008 update published (2000 prior version), with 2 important additions: 1) Pre-registration of clinical trials WHO registrye ( others European Clinical trials must also have a registered Eudra CT number 2) Post-study access by study subjects to interventions identified as beneficial in the study or access to other appropriate care or benefits should be described in the protocol

6 ICH-GCP: Lecture Outline ICH-GCP History ICH-GCP Principles Ethics Committee Responsibilities Investigator Responsibilities Patient Safety

7 ICH-GCP Purpose 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

8 ICH-GCP Principles Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s)

9 ICH-GCP Principles Before a trial is initiated, forseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks

10 ICH-GCP Principles The rights, safety, and well-being of the trial subject are the most important considerations and should prevail over interests of science and society

11 ICH-GCP Principles The available nonclinical and clinical information on an investigational product should be adequate to support the proposed trial

12 ICH-GCP Principles Clinical trials should be scientifically sound, and described in a clear, detailed protocol

13 ICH-GCP Principles A trial should be conducted in compliance with the protocol that has received prior independent ethics committee approval

14 ICH-GCP Principles The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist

15 ICH-GCP Principles Each individual involved in a trial should be qualified by education, training, and experience to perform his or her respective task(s)

16 ICH-GCP Principles Freely informed consent should be obtained from every subject prior to clinical trial participation

17 ICH-GCP Principles All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification

18 ICH-GCP Principles The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the regulatory requirement(s)

19 ICH-GCP Principles Investigational products should be manufactured, handled, and stored in accordance with good manufacturing practice (GMP). They should be used in accordance with the approved protocol

20 ICH-GCP Principles Systems with procedures that assure the quality of every aspect of the trial should be implemented [Standard Operating Procedures: SOPs]

21 ICH-GCP: Lecture Outline ICH-GCP History ICH-GCP Principles Ethics Committee Responsibilities: see S. O Neill Investigator Responsibilities Patient Safety

22 ICH-GCP: Lecture Outline ICH-GCP History ICH-GCP Principles Ethics Committee Responsibilities Investigator Responsibilities Patient Safety

23 Investigator Responsibilities Qualified investigator Familiar with product and protocol Comply with GMP and other regulatory requirements Demonstrate potential for suitable recruitment Maintain list of delegated duties and associated individuals, and ensure that all are appropriately qualified and informed Written IEC approval before commencing trial

24 Investigator Responsibilities: Informed Consent Comply with ethical principles (Declaration of Helsinki) All subjects should be fully informed Neither the investigator, nor the trial staff, should coerce or unduly influence a subject to participate or to continue to participate in a trial Prior to a subject s participation in a trial, the written informed consent form should be signed and personally dated by the subject or the subject s legally accpted representative, and by the person who conducted the informed consent discussion. A copy should be received by the subject

25 Investigator Responsibilities: During Trial Conduct the trial in compliance with the protocol (signed to confirm) Permit monitoring and auditing by sponsor and inspection by appropriate regulatory authorities A qualified physician who is an investigator or sub-investigator should be responsible for all trial-related medical decisions It is recommended that the investigator inform the subject s primary physician Although a subject is not obliged to give his/her reason(s) for withdrawing prematurely from a trial, the investigator should make a reasonable effort to ascertain the reason(s) The investigator is responsible for drug accountability at the trial site The investigator should document and explain any protocol violations or deviations, or if blinding is broken

26 Investigator Responsibilities: Records & Reports Ensure the accuracy, completeness, legibility and timeliness of the data reported to the sponsor in the case report forms (CRFs) All data on CRFs from source documents should be consistent Should make available for direct access all requested trial-related records All SAEs should be reported immediately to the sponsor

27 Investigator Responsibilities: Post-Trial Upon completion of the trial, the investigator should inform the institution (where applicable) The investigator should provide the Institutional Ethics Committee (IEC) with a summary of the trial s outcome, and the regulatory authorities with any reports required Essential documents should be retained for at least 2 years post licence approval

28 ICH-GCP: Lecture Outline ICH-GCP History ICH-GCP Principles Ethics Committee Responsibilities Investigator Responsibilities Patient Safety

29 Patient Safety Adverse Event (AE) Definitions & Investigator Responsibilities for Safety Reporting Adverse Event (AE): any untoward medical occurrence in a patient or clinical investigation subject who has taken a pharmaceutical product (and which does not necessarily have causal relationship with this treatment) All AEs must be recorded in the case report form, even if the event is commonly observed Laboratory abnormalities may also be classified as AEs Adverse Reaction (AR): an adverse event with a reasonable causal relationship with treatment

30 Patient Safety Adverse Event (AE) Definitions & Investigator Responsibilities for Safety Reporting Serious Adverse Event (SAE): any untoward medical occurrence in a patient or clinical investigation subject that at any dose results in: Death Is life threatening Requires patient hospitalisation, or prolongation of existing hospitalisation Results in persistent or significant disability Is a congenital anomaly/birth defect Report all SAEs to Sponsor (Company, Other) immediately (<24 hours), and to regulatory agencies (IMB, EMEA) within 7 days

31 Patient Safety Adverse Event (AE) Definitions & Investigator Responsibilities for Safety Reporting Serious Adverse Reaction (SAR): a serious adverse event with a reasonable causal relationship with treatment Suspected Serious Adverse Reaction (SSAR) Suspected Unexpected Serious Adverse Reaction (SUSAR)

32 Adverse Event Classificiation AE SAE AR SAR Unexpected Expected Life-Threatening/ Death Congenital anomaly Hospitalisation Disability From: ICRIN GCP Course Syllabus, April, 2009

33 Summary: ICH-GCP ICH-GCP History ICH-GCP Principles Ethics Committee Responsibilities (see S. O Neill) Investigator Responsibilities Patient Safety