Good Clinical Practice (GCP)

Prof. Medhat Faris

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Agenda

• Introduction• Objectives• Historical perspective• ICH• Principles of GCP• IRB/Ethical committee• Informed consent• Clinical Investigators

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Introduction• This presentation is designed for physicians andcoordinators needing an overview of GoodClinical Practice (GCP) as it relates to theirparticipation in clinical trials

• The participant will understand• The need for and purpose of GCP.• The rationale and content of ICH guidelines.• The role of ICH GCP in validating uniformity of data collection and analysis.

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Good Clinical Practice (GCP)

The international ethical and scientific qualitystandard for designing, conducting, recordingand reporting trials that involve human subjects.

Compliance with this standard providesassurances that the rights, safety and well-beingof the trial subjects are protected and the dataand reported results are credible and accurate.

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Historical Perspective

• Nuremberg Code

• Kefauver-Harris Amendment

• Declaration of Helsinki

• International Conference on Harmonization (ICH)

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Nuremberg Code (1948)

• A set of research ethics principles forhuman experimentation set as a result of theNuremberg Trials at the end of the WW II

• The experiments resulted in death,disfigurement or permanent disability

• Ten points of the Nuremberg Code

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Kefauver-Harris (KH) Amendment (1962)• Enacted following the Thalidomide tragedies in Europe.

• Thousands of infants exposed during pregnancy developed with severe limb deformities.

• KH Amendment required drug trials and drug advertisingto document and discuss efficacy and safety data.

• It introduced a "proof-of-efficacy“ requirement, that was not present before.

• Finally, cheap generic drugs could no longer be marketed as expensive drugs under new trade names.

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Declaration of Helsinki (1964)

• International guidance developed by the WorldMedical Association that compiled ethical, clinical,and scientific principles.

• The basic principles of GCP consisting of 12 basic principles. Initiated in 1964 and amended 4 times

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International Conference on Harmonization (ICH)

• An international body, formed in 1990, thatregulates clinical trials involving human subjects.

• Developed to internationalize and standardizeclinical Trials.

• Representatives from industry, government,regulatory agencies and academia combined todiscuss international, minimal standards ofconduct and testing of products.

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ICH GCP Guidance Objective

• Provide a unified standard for theEuropean Union (EU), Japan, and theUnited States to facilitate the mutualacceptance of clinical data by theregulatory agencies of those involved.

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Principles of GCP1. Clinical trials should be conducted in accordance

with the ethical principles of the Declaration ofHelsinki, which are consistent with GCP and theapplicable regulatory requirement(s).

2. Before a trial is initiated, potential risks andinconveniences should be weighed against theanticipated benefit for the individual trial subjectand society.

A trial should be initiated and continued only if the anticipated benefits justify the risks.

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Principles of GCP (Cont)

3- The rights, safety and well being of the trialsubjects are the most important considerationand should prevail over interests of scienceand society.

4- The available non-clinical and clinicalinformation on an investigational productshould be adequate to support the proposedclinical trial.

5- Clinical trials should be scientifically sound,and described in a clear, detailed protocol.

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Principles of GCP (cont)

6- A trial should be conducted in compliance withthe protocols that have received prior InstitutionalReview Board (IRB)/Independent ethics committee(IEC) approval

7- The medical care given to, and medicaldecisions made on behalf of, subjects shouldalways be the responsibility of a qualified physicianor, when appropriate, of a qualified dentist.

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8- Each individual involved in conducting a trialshould be qualified by education, training andexperience to conduct or perform the respectivetask.

9- Freely given informed consent should beobtained from every subject prior to clinical trialparticipation.

10- All clinical trial information should be recorded,handled, and stored in a way that allows itsaccurate reporting, interpretation and verification

Principles of GCP (cont)

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11- The confidentiality of the subjects should beprotected.

12- Investigational products should bemanufactured, handled, and stored in accordanceof good manufacturing practice (GMP) and theyshould be used in accordance with the approvedprotocol.

13- Systems with procedures that assure thequality of every aspect of the trial should beimplemented.

Principles of GCP (cont)

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Institutional Review Board (IRB)Independent Ethics Committee (IEC)

• A• A formally designated group that oversees

research involving human subjects.

• Approves and disapproves human subjectresearch.

• According to the standards of the community or theinstitution, the IRB/IEC may require modificationsto a protocol to ensure patient safety.

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IRB Function

• The primary function of an IRB/IEC is tosafeguard the rights, safety, and wellbeing of all trial subjects. This isaccomplished by initial, continuing andannual review.

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IRB Review Documents1. Investigator qualifications – Curriculum Vitae (CV) and/or prior experience.

2. Protocol and any changes or amendments.

3. Written informed consent forms and any changes during the trial.

4. Recruitment procedures (including advertisements)

5. Written information to be given to the subjects.

6. Investigator’s Brochure (IB).

7. Available safety information.

8. Patient compensation.

9. Other materials that affect patient safety and willingness to participate.

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IRB Memberds

• An IRB should consist of members whocollectively have the qualifications andexperience to review and evaluate thescience, medical aspects, and ethics ofthe proposed trial.

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IRB Members (cont)1. A minimum of five (5) members.

2. One member whose concern is not scientific.

3. One member who has no personal or familial relationship to the institution or trial site.

4. Any member with a conflict of interest may not participate in any part of the review or vote (except to provide requested information).

5. Individuals with special expertise may be invited to assist with areas of unique or complex nature. These will not be voting members.

6. A list of IRB/IEC members and their qualifications should be maintained. M Faris 2010

Informed Consent Form (ICF)

• Legally effective informed consent is thebeginning event of a clinical trial.

• It is the responsibility of the principal investigatorto provide a document that satisfies basicelements and any applicable additional elements.

• It may be written or verbal.

• Subject should be given the information withample time and opportunity to make a decision.Participating parties should minimize conflict of .

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ICF (cont)

• Informed Consent may not include anylanguage or verbal intimation that wouldcause the subject to waive any legalrights. The consent does not releasethose conducting or sponsoring the trialfrom any liability or negligence.

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Basic Elements of the ICF1. The purpose of the study, the expected duration of

participation, a description of study procedures andidentification of anything that is experimental.

2. Any reasonably expected risks or discomforts

3. Benefits to the subject or others, if any, that canreasonably be expected.

4. Alternate therapies, if any, that might benefit the subject.

5. Description of confidentiality measures to protectsubject identity.

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Basic Elements of the ICF (Cont)

6- For research involving more than minimal risk,a description of available compensation andmedical treatments, available if injury occursduring the treatment.

7- Whom to contact for questions about researchand research subject rights. A statement ofwhom to contact for research related injury.

8-Statement that participation is voluntary andassurance that there is no penalty or loss ofbenefits for refusal to participate.

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Additional Elements of ICF1. A particular treatment or procedure may

involve risk to the subject (or the embryo orfoetus, if the subject is or may becomepregnant) that is currently unforeseeable.

2. Possible circumstances under which thesubjects participation may be terminated bythe investigator without regard to thesubjects consent.

3. Additional cost (potential) to subject forresearch participation

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Additional Elements of ICF (cont)

4. Consequences of subject withdrawal from theresearch and procedures for withdrawal.

5. Assurance that significant new findingsduring the course of the research, which mayaffect the subjects willingness to continue,will be provided to the subject.

6. Approximate number of subjects in the study.

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Clinical Investigators• They should be qualified by education,

training, and experience to assumeresponsibility for the proper conduct ofthe trial.

• The evidence of qualifications should bean up-to-date Curriculum Vitae (CV)and/or other relevant documentation.

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Investigator Responsibilities

• Implement the Protocol

• Minimize Bias, Conflict and Failure

• Medical Care of Subjects

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Implementing the Protocol

• The investigator should be completelyfamiliar with the protocol and investigationalproduct (IB, protocol and other trialinformation).

• Investigator should know/comply with GCP /regulatory requirements

• Maintain a list of delegated tasks, duties andpersonnel to whom there has been delegatedtrial-related tasks.

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Minimize Bias, Conflict, Failure• Investigator must permit monitoring and

inspections by sponsors and regulatory agencies.

• Investigator should have adequate resources(patients / staff) and facilities (space / equipment)to conduct the trial as required.

• Investigator should have adequate time toconduct, train, and oversee the activities of the

trial.

• Investigator should oversee and verify thatdesignees and co-participants are adequatelytrained in the trial.

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Medical Care of Subjects• A qualified physician, investigator or sub-investigator should be

responsible for all trial-related medical decisions.

• During and after subject participation, the investigator/institutionshould ensure adequate medical care for any adverse events.

• Investigators should inform a subject when medical care isneeded for intercurrent illness(es) of which the investigatorbecomes aware.

• Primary physicians should be notified about a subject’sparticipation in a trial if the subject agrees to the

notification.

• Investigators should make a reasonable effort to ascertainwhy subjects withdraw from a trial. Patients are not obligedin any way to provide reasons for withdrawal.

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THANK YOU