© 2004 Aeras Global TB Vaccine Foundation Intermediate Clinical Research Clinical Research Practice 2.

© 2004 Aeras Global TB Vaccine © 2004 Aeras Global TB Vaccine FoundationFoundation

Intermediate Clinical Intermediate Clinical ResearchResearch

Clinical Research Clinical Research Practice 2Practice 2

22 22© 2005 Aeras Global TB Vaccine Foundation© 2005 Aeras Global TB Vaccine Foundation

Purpose:Purpose:

To provide an in depth understanding To provide an in depth understanding ofof

Good Clinical Practice and ethical Good Clinical Practice and ethical guidelinesguidelines

for clinical research and the protection for clinical research and the protection ofof

research participants. research participants.


In This Course You Will Learn In This Course You Will Learn To:To:

Identify the key events and documents that Identify the key events and documents that led to the standards and ethical principles that led to the standards and ethical principles that guides the conduct of clinical research today.guides the conduct of clinical research today.

Recognise the key factors or guidelines for Recognise the key factors or guidelines for clinical research that emerged from the clinical research that emerged from the primary events or documents that guides primary events or documents that guides current clinical research ethics. current clinical research ethics.

Name the key international guidelines that Name the key international guidelines that were adopted and followed as part of the were adopted and followed as part of the South African guidelines for the conduct of South African guidelines for the conduct of clinical research.clinical research.

Identify special populations that have Identify special populations that have additional guidelines for their protection additional guidelines for their protection during clinical research under SA GCP during clinical research under SA GCP guidelines.guidelines.


In This Course You Will Learn In This Course You Will Learn To:To:

Describe the guidelines for the inclusion of children Describe the guidelines for the inclusion of children and adolescents and vulnerable communities in and adolescents and vulnerable communities in clinical research.clinical research.

List the 4 primary means of protection offered to List the 4 primary means of protection offered to study participants under GCP guidelines throughout study participants under GCP guidelines throughout the conduct of a study. the conduct of a study.

Identify the 4 phases of clinical trials.Identify the 4 phases of clinical trials.

Identify who is responsible for ensuring that research Identify who is responsible for ensuring that research is performed and data generated in compliance with is performed and data generated in compliance with GCP guidelines and other applicable regulations.GCP guidelines and other applicable regulations.


Do You Remember?Do You Remember?

What is clinical research?What is clinical research?

Why do we perform it?Why do we perform it?

What happens in clinical What happens in clinical research?research?


What Is Clinical Research?What Is Clinical Research?

A scientific study looking for answers A scientific study looking for answers to specific questions.to specific questions.

Method for finding safe, new and Method for finding safe, new and improved vaccines, drugs, and other improved vaccines, drugs, and other treatments to improve health.treatments to improve health.

Research that relies on human Research that relies on human volunteers.volunteers.


Why Do We PerformWhy Do We PerformClinical Research?Clinical Research?

Test new therapies and drugs.Test new therapies and drugs. Gather data from participants who have Gather data from participants who have

had a known intervention and monitor had a known intervention and monitor results.results.

Determine the safety and effectiveness of Determine the safety and effectiveness of drugs, therapies, and other treatments.drugs, therapies, and other treatments.

Develop new drugs and treatments that Develop new drugs and treatments that are safer, more effective and faster are safer, more effective and faster working than any before.working than any before.

Ultimately – to improve health status.Ultimately – to improve health status.


Define Research Define Research Question Question (What do you want to know?)(What do you want to know?)

The Life Cycle Of The Life Cycle Of A Clinical Research ProjectA Clinical Research Project

Write a Write a ResearcResearchhProposalProposalFind Funding & Find Funding &

Select Research Select Research TeamTeam

Write Write ProtocolProtocol

Conduct Conduct ResearcResearc

hh

Analyse Analyse ResultsResults

Report Report ResultsResults

Get RegulatoryGet Regulatory

ApprovalApproval


Study or Trial?Study or Trial?

All trials are studies but not all studies are All trials are studies but not all studies are trials.trials.

Do you know what the difference is?Do you know what the difference is?

During a clinical trial a specific During a clinical trial a specific interventionintervention needs to be needs to be testedtested on humans. on humans.

Which of the studies at our site can be Which of the studies at our site can be classified as trials? classified as trials?

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© 2005 Aeras Global TB Vaccine Foundation© 2005 Aeras Global TB Vaccine Foundation

Four Phases of Clinical TrialsFour Phases of Clinical TrialsTrials with a drug safety aspect has to Trials with a drug safety aspect has to go through the following phases, go through the following phases, before making the drug or vaccine before making the drug or vaccine widely available to the public.widely available to the public.

PhaseI

Phase II

Phase III

Phase IV

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Phase IPhase I

New drugs/treatment are tested on New drugs/treatment are tested on humans for the first time.humans for the first time.

Small group of volunteers (30-50)Small group of volunteers (30-50) Healthy : 21+ years of ageHealthy : 21+ years of age GoalGoal: Determine the effect of the : Determine the effect of the

drug on a person’s body at a drug on a person’s body at a physical/physiological level.physical/physiological level.

““Is the treatment safe ?”Is the treatment safe ?”

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Phase IIPhase II Phase I completed = treatment safe thus farPhase I completed = treatment safe thus far Less than 100 VolunteersLess than 100 Volunteers Disease specific volunteersDisease specific volunteers Conduct Randomised trials in order to Conduct Randomised trials in order to

compare the Experimental drug with a compare the Experimental drug with a Placebo or the standard treatment.Placebo or the standard treatment.

GoalGoal: Determine safety and efficacy. How it : Determine safety and efficacy. How it should be given, how often and how much is should be given, how often and how much is safe?safe?

““Can the treatment work ?”Can the treatment work ?”

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Phase IIIPhase III

Phase II completedPhase II completed Hundreds - thousands of volunteersHundreds - thousands of volunteers Conduct Randomised and Blinded studies.Conduct Randomised and Blinded studies. GoalGoal: Determine safety, efficacy, benefits : Determine safety, efficacy, benefits

and the range of possible adverse and the range of possible adverse reactions in the broader community.reactions in the broader community.

Approval for the market.Approval for the market. ““Is the new treatment better than existing Is the new treatment better than existing

treatment or placebo?”treatment or placebo?”

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Phase IVPhase IV

Post marketPost market Hundreds - thousands of volunteersHundreds - thousands of volunteers GoalGoal: Determine additional : Determine additional

information including the drug’s information including the drug’s risks, benefits, and optimal use.risks, benefits, and optimal use.

““Is there a better way to use this Is there a better way to use this treatment ?”treatment ?”

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It does not matter what type or It does not matter what type or kind of clinical research we kind of clinical research we

conduct. conduct.

If there are humans involved in If there are humans involved in the research there is one the research there is one

condition that absolutely has condition that absolutely has to be met.to be met.

Do you know what it is?Do you know what it is?

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Protection of Human Protection of Human ParticipantsParticipants

Good Clinical Practice Good Laboratory Practice

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Good Clinical PracticeGood Clinical Practice

An international ethical and scientific An international ethical and scientific quality standard for designing, conducting, quality standard for designing, conducting, recording and reporting trials that involve recording and reporting trials that involve the participation of human volunteers.the participation of human volunteers.

Simply put …. Simply put …. GCP is the set of rules by GCP is the set of rules by which we conduct our research.which we conduct our research.

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Good Laboratory PracticeGood Laboratory Practice

Represents a set of principles that provides a Represents a set of principles that provides a framework within which laboratory studies are framework within which laboratory studies are planned, performed, monitored, recorded, planned, performed, monitored, recorded, reported and archived.reported and archived.

Simply put …. Simply put ….

GLP is the set of rules of research in the lab.GLP is the set of rules of research in the lab.

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Why Is Following GCP and GLPWhy Is Following GCP and GLP Important ? Important ?

Compliance with these standards Compliance with these standards assures:assures:

participant rights are protected.participant rights are protected. the safety of human volunteers.the safety of human volunteers. participant well-being is a priority.participant well-being is a priority. results are used for improvement of results are used for improvement of

health and well-being of all.health and well-being of all.

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The Protection of Human The Protection of Human ParticipantsParticipants

An introduction to GCP and GLP is not An introduction to GCP and GLP is not enough to understand the complexities of enough to understand the complexities of the ways in which the Human Research the ways in which the Human Research Participant must be protected.Participant must be protected.

We need to look at the codes, declarations, We need to look at the codes, declarations, reports and guidelines that provides the:reports and guidelines that provides the: Ethical rules and principals andEthical rules and principals and Foundational elements…….Foundational elements…….

……………….for the conduct of clinical research..for the conduct of clinical research.

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So, ……..So, ……..

In the past there were abuses and In the past there were abuses and unethical behavior. Science was put unethical behavior. Science was put ahead of human rights,ahead of human rights,

and the..and the.. International community responded – International community responded –

new standards emerged. new standards emerged.

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In the CRP 1 ModuleIn the CRP 1 Module

We looked at the We looked at the Nuremberg CodeNuremberg Code Declaration of HelsinkiDeclaration of Helsinki Belmont ReportBelmont Report ICH GCP………..ICH GCP………..

Let’s dig a bit deeper into a bit more Let’s dig a bit deeper into a bit more detail..detail..

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History of the Nuremberg History of the Nuremberg Code:Code:

Nazi Medical War Crimes:Nazi Medical War Crimes: 1939 – 1945 1939 – 1945

Photos courtesy of US Holocaust Museum

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Nazi Experiments Using Nazi Experiments Using Children:Children:

1939 - 19451939 - 1945

Photos courtesy of US Holocaust Museum

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The Nuremberg TrialThe Nuremberg Trial

1946: 23 Nazi 1946: 23 Nazi physicians on trial.physicians on trial.

““Permissible Permissible Medical Medical Experiments” Experiments”

The Nuremberg The Nuremberg CodeCode

Photo courtesy of USHMM.

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Nuremberg CodeNuremberg Code Published in 1947Published in 1947 The first The first internationallyinternationally recognized recognized

standardstandard for human participant for human participant research.research.

Consisted of 10 conditions and included:Consisted of 10 conditions and included: Voluntary consent Voluntary consent Risk/benefit ratioRisk/benefit ratio Right to withdraw from experiments.Right to withdraw from experiments.

These conditions had to be met before These conditions had to be met before research was ethically permissible.research was ethically permissible.

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History of the History of the Declaration of HelsinkiDeclaration of Helsinki

Thalidomide disaster – late 1950’sThalidomide disaster – late 1950’s

Results of this tragedy:Results of this tragedy: FDA requiring pre-clinical safety reportsFDA requiring pre-clinical safety reports Europe and UK developed reporting Europe and UK developed reporting

systemssystems

Led to the Led to the Declaration of Helsinki Declaration of Helsinki

in 1964in 1964

Photo courtesy of The Teratology Society

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World Medical Association World Medical Association Declaration of HelsinkiDeclaration of Helsinki

Developed by the World Medical Developed by the World Medical Association in 1964. Association in 1964.

First significant effort of the medical First significant effort of the medical community to regulate itself.community to regulate itself.

Legally binding.Legally binding.

Latest version: October 2000 with notes of Latest version: October 2000 with notes of clarification in 2002 & 2004. clarification in 2002 & 2004.

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Declaration of Helsinki Declaration of Helsinki (DOH)(DOH)

Consists of 32 ethical principles and Consists of 32 ethical principles and includes:includes: Voluntary consent , Risk/benefit ratio and Voluntary consent , Risk/benefit ratio and

the Right to withdraw from the Right to withdraw from experiments……experiments……

andand Additional principles for medical research Additional principles for medical research

combined with medical care.combined with medical care. Use of placebo.Use of placebo. Access of participants to the best proven Access of participants to the best proven

methods identified by the study.methods identified by the study.

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History of the Belmont History of the Belmont Report:Report:

Tuskegee Syphilis Study: 1932-1972Tuskegee Syphilis Study: 1932-1972

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“This examination is a very special one and after it is finished you will be given a special treatment if it is believed you are in a condition to stand it.”

“This is your last chance for special free treatment.”

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This was one This was one of the of the strategies strategies used to keep used to keep the the participants participants happy.happy.

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Then the Tuskegee Study Then the Tuskegee Study Became Public and …… Became Public and ……

National commission – 1974National commission – 1974

Published the “Published the “Ethical Principles Ethical Principles and guidelines for the Protection and guidelines for the Protection of Human Subjects.” -1979of Human Subjects.” -1979

Belmont Report Belmont Report

Identified three basic principles.Identified three basic principles.

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Respect for Persons

Individuals should be treated as autonomous agents

Persons with diminished autonomy are entitled to protection.

Informed Consent

Participants, to the degree that they are capable, must be given the opportunity to choose what shall or shall not happen to them.

Key required elements: Information Comprehension Voluntary

participation

Principle Principle ApplicationApplication

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Beneficence

Human participants should be treated in an ethical manner and protected from harm.

Research should maximize possible benefits and minimize possible harm.

Assessment of Risk and Benefit

The nature and scope of risks and benefits must be assessed and balanced in a systematic manner.


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Justice

The benefits and risks of research must be distributed fairly and without bias.

Selection of Participants

There must be fair procedures and outcomes in the selection of research participants.


Last 3 slides : Courtesy of the Claremont Graduate University: History of Ethics

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Did the Nuremberg Code & the Did the Nuremberg Code & the Declaration of Helsinki Change Declaration of Helsinki Change the Conduct of Clinical the Conduct of Clinical Research?Research?

NO !NO !

The Research Community needed something to:The Research Community needed something to:

Ensure that the rights, safety and well-being of trial Ensure that the rights, safety and well-being of trial participants are protectedparticipants are protected

Ensure the credibility of clinical trial dataEnsure the credibility of clinical trial data

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So, What Happened ?So, What Happened ?

Belmont Report - 1979Belmont Report - 1979

ICH GCP - 1990ICH GCP - 1990

CIOMS - 1993CIOMS - 1993

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International Conference on International Conference on Harmonization 1990Harmonization 1990

World Health Organisation (WHO) – planned to World Health Organisation (WHO) – planned to standardise requirements for registration of standardise requirements for registration of new drugs:new drugs: Many sets of guidelines all over the world.Many sets of guidelines all over the world. High cost of clinical trials and ethical High cost of clinical trials and ethical

considerations of repeating trials when drug considerations of repeating trials when drug efficacy was already demonstrated. efficacy was already demonstrated.

International Conference on International Conference on HarmonizationHarmonization in 1990 – Brussels in 1990 – Brussels

Published the ICH Published the ICH GCP GuidelinesGCP Guidelines

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What Does ICH GCP Cover?What Does ICH GCP Cover?

Consists of 13 PrinciplesConsists of 13 Principles Covers guidelines for the conduct of Covers guidelines for the conduct of

research:research: EthicsEthics Essential documentsEssential documents InvestigatorInvestigator ProtocolProtocol Investigator’s BrochureInvestigator’s Brochure SponsorSponsor

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The Establishment of CIOMSThe Establishment of CIOMS

Council for International Organizations Council for International Organizations of Medical Sciencesof Medical Sciences

Established jointly by WHO and United Established jointly by WHO and United Nations Educational, Scientific and Nations Educational, Scientific and Cultural Organisation (UNESCO) in 1949Cultural Organisation (UNESCO) in 1949

GuidelinesGuidelines on how to on how to effectively applyeffectively apply the ethical principles as set forth in the the ethical principles as set forth in the DOHDOH. .

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CIOMS GuidelinesCIOMS Guidelines

Consists of 15 guidelines that Consists of 15 guidelines that includes:includes: Informed consentInformed consent Standards for external reviewStandards for external review Recruitment of participants Recruitment of participants

………….focuses on research sponsored .focuses on research sponsored by or initiated in developed by or initiated in developed countries and carried out in countries and carried out in developing countriesdeveloping countries

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Do you recognise these

elements?

GCP and National GCP and National DifferencesDifferences

GCP is universal, but each country has its own regulations GCP is universal, but each country has its own regulations and agencies to ensure GCP compliance. and agencies to ensure GCP compliance.

In the United States, GCP is implemented under In the United States, GCP is implemented under 45 CFR Part 46, under the U.S. Code of Federal Regulations 45 CFR Part 46, under the U.S. Code of Federal Regulations for the Protection of Human Subjects.for the Protection of Human Subjects.

Defines the Institutional Review Board.Defines the Institutional Review Board. Provides guidelines for informed consent.Provides guidelines for informed consent.

The U.S. 45 CFR Part 46 is only be applicable in South The U.S. 45 CFR Part 46 is only be applicable in South Africa Africa if if a study is U.S. funded or otherwise subject to U.S. a study is U.S. funded or otherwise subject to U.S. regulations. regulations.

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Clinical Trial Approval in SAClinical Trial Approval in SA Standard Approval Process:Standard Approval Process:

1.1. MCC (Regulatory Authority)MCC (Regulatory Authority)2.2. Ethics Committee ApprovalEthics Committee Approval

Multi-Centre StudiesMulti-Centre Studies “ “It is It is unacceptableunacceptable for for developed country developed country

participantsparticipants to have to have better standards of care better standards of care offeredoffered in the study when in the study when compared to South compared to South African participantsAfrican participants. When South Africa is . When South Africa is chosen for a clinical trial while the trial is not chosen for a clinical trial while the trial is not undertaken in the country of origin an undertaken in the country of origin an explanation should be sought about why this is explanation should be sought about why this is the case.” the case.” SA GCP GuidelinesSA GCP Guidelines

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Documents that Guide the Documents that Guide the Conduct of Clinical Research in Conduct of Clinical Research in South Africa:South Africa:

Declaration of Helsinki -2000Declaration of Helsinki -2000

ICH Guidelines for Good Clinical PracticeICH Guidelines for Good Clinical Practice (International Conference on Harmonization)(International Conference on Harmonization)

CIOMS CIOMS (Council for International Organizations of (Council for International Organizations of Medical Sciences)Medical Sciences)““International Guidelines for Biomedical Research International Guidelines for Biomedical Research Involving Human Subjects” – 1993Involving Human Subjects” – 1993

These are the documents that ensure the welfare These are the documents that ensure the welfare and integrity of participants in SA and must be and integrity of participants in SA and must be

followed by the principle investigator.followed by the principle investigator.““Guidelines for Good Practice in the conduct of Clinical Trials in Human Participants in South Africa” by the Dept.of HealthGuidelines for Good Practice in the conduct of Clinical Trials in Human Participants in South Africa” by the Dept.of Health

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Do We Have a SA GCP ?Do We Have a SA GCP ?

““Guidelines for Good Practice in the Conduct Guidelines for Good Practice in the Conduct of Clinical Trials in Human Participants in of Clinical Trials in Human Participants in

South Africa”South Africa”

The purpose of these guidelines is to The purpose of these guidelines is to provide provide South Africa with clearly South Africa with clearly articulated articulated standardsstandards of good clinical of good clinical practice practice in researchin research that are also that are also relevant relevant to to locallocal realities and contexts. realities and contexts.

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ACTIVITYACTIVITY

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How are Vulnerable Research How are Vulnerable Research Participants Protected?Participants Protected?

Some research participants are classified Some research participants are classified as as Vulnerable Research ParticipantsVulnerable Research Participants who who areare relativelyrelatively or or absolutely incapableabsolutely incapable of of protecting their own interests.protecting their own interests.

The research team should be aware of The research team should be aware of the special problems of research the special problems of research involving vulnerable populationsinvolving vulnerable populations

Is the Research Justified?Is the Research Justified? Must offer additional safeguards for Must offer additional safeguards for

their safety and welfare.their safety and welfare.

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Special Populations of Special Populations of ParticipantsParticipants

1.1. Children and Children and AdolescentsAdolescents

2.2. Women and Women and pregnancypregnancy

3.3. Pregnant Women Pregnant Women

4.4. Fetuses Fetuses in uteroin utero

5.5. Fetuses Fetuses ex uteroex utero

6.6. PrisonersPrisoners

7.7. Mental disabilityMental disability

8.8. Vulnerable Vulnerable communitiescommunities

9.9. Other special Other special GroupsGroups

From the Guidelines for Good Practice in the conduct of clinical trials in Human Participant in

South Africa. 2.3

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Some Specific Guidelines in Some Specific Guidelines in Order to Further Protect…..Order to Further Protect…..

Children and AdolescentsChildren and Adolescents Does not place the child Does not place the child

in no greater than in no greater than Minimal RisksMinimal Risks

If more than Minimal If more than Minimal Risk - Direct Benefit for Risk - Direct Benefit for childchild

Need Consent and Need Consent and Assent Assent

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Children in Research: MinorsChildren in Research: Minors

South African Law:South African Law:

Minor:Minor: Unmarried person below age 21 Unmarried person below age 21

1 JULY 2007 CHANGED TO 18!1 JULY 2007 CHANGED TO 18!The consent of a parent/legal guardian The consent of a parent/legal guardian

should be obtained for any research should be obtained for any research procedure involving a minor.procedure involving a minor.

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Assent In Addition to Assent In Addition to ConsentConsent

Out of Respect for Children/Adolescents as Out of Respect for Children/Adolescents as a developing person, children should be a developing person, children should be asked whether or not they wish to asked whether or not they wish to participate.participate.

Assent: Assent: A willingness that does notA willingness that does not necessarily carry the greater necessarily carry the greater understanding and legal understanding and legal implicationsimplications that are generally understood by that are generally understood by ‘consent’. ‘consent’.

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Some Specific Guidelines In Some Specific Guidelines In Order to Further Protect…..Order to Further Protect…..

Vulnerable CommunitiesVulnerable Communities Could this research not be carried out in Could this research not be carried out in

populations from developed communities?populations from developed communities? The research must be responsive to the The research must be responsive to the

health needs and the priorities of the health needs and the priorities of the community.community.

Consent: content, languages and proceduresConsent: content, languages and procedures Should not adversely affect the routine Should not adversely affect the routine

treatment of patients.treatment of patients.

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Ongoing Protection Throughout Ongoing Protection Throughout the Studythe Study

As researcher/team we now have:As researcher/team we now have: Approval of the study Approval of the study Signed consent documentSigned consent document

ButBut

In clinical research, the commitment to In clinical research, the commitment to participants is to participants is to safeguardsafeguard their their interests throughout the study.interests throughout the study.

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Four Primary Means of Four Primary Means of Participant ProtectionParticipant Protection

Methods to protect our participants:Methods to protect our participants:

1.1. Ongoing Informed ConsentOngoing Informed Consent

2.2. Safety ReportingSafety Reporting

3.3. Data and Safety MonitoringData and Safety Monitoring

4.4. Continuing IRB ReviewContinuing IRB Review

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1: Ongoing Informed 1: Ongoing Informed ConsentConsent

Informed consent is an ongoing Informed consent is an ongoing

communication process during the entire communication process during the entire study.study.

The participant should maintain the ability The participant should maintain the ability to understand and that he/she may to understand and that he/she may withdraw from the study at any time.withdraw from the study at any time.

Additional Informed Consent (re-consent) Additional Informed Consent (re-consent) should occur when:should occur when: There are changes in the studyThere are changes in the study There is new information that may affect the There is new information that may affect the

willingness to participate further.willingness to participate further.

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2: Safety Reporting2: Safety Reporting

Further ongoing protection of our Further ongoing protection of our participants is to participants is to reportreport on any ill on any ill “effect” of our intervention/drug on “effect” of our intervention/drug on our participants.our participants.

We call this Adverse Event reporting.We call this Adverse Event reporting.

The process will be detailed in the The process will be detailed in the study protocol.study protocol.

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Adverse Event (AE)Adverse Event (AE)

““Any untoward medical occurrence in Any untoward medical occurrence in a patient or clinical investigation a patient or clinical investigation subject administered a subject administered a pharmaceutical product and which pharmaceutical product and which does not necessarily have a causal does not necessarily have a causal relationship with this treatment.”relationship with this treatment.”

(ICH GCP 1.2)(ICH GCP 1.2)

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Adverse Drug Reaction Adverse Drug Reaction (ADR)(ADR)

““All noxious and unintended responses All noxious and unintended responses to a medicinal product related to any to a medicinal product related to any dose should be considered adverse dose should be considered adverse drug reactions.” drug reactions.” (ICH GCP 1.1)(ICH GCP 1.1)

Expected:Previously observed events

Unexpected:Any AE that is not expected

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Serious Adverse Event (SAE)Serious Adverse Event (SAE)

““Any untoward medical occurrence that at Any untoward medical occurrence that at any dose:any dose:

Results in death.Results in death. Is life-threatening.Is life-threatening. Requires inpatient hospitalization or Requires inpatient hospitalization or

prolongation of existing hospitalisation.prolongation of existing hospitalisation. Results in persistent or significant Results in persistent or significant

disability/incapacity ordisability/incapacity or Is a congenital anomaly/birth defect.” Is a congenital anomaly/birth defect.” (ICH (ICH

GCP 1.50)GCP 1.50)

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3: Data and Safety 3: Data and Safety MonitoringMonitoring

Independent CommitteeIndependent CommitteeEssential role :Essential role : in protecting the safety of participants in protecting the safety of participants and ensuring integrity of the research studyand ensuring integrity of the research study

The Data Safety Monitoring Board (DSMB)The Data Safety Monitoring Board (DSMB)can and will stop a study if:can and will stop a study if:

1. There are safety concerns. 1. There are safety concerns. 2. The objectives of the study are met.2. The objectives of the study are met.STO

P

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4: Continuing IRB Review4: Continuing IRB Review Annual Reports to the Annual Reports to the

IRB from the regulatory IRB from the regulatory officer of the study.officer of the study.

Reports from the DSMB.Reports from the DSMB.

Depending on the Depending on the degree of risk to degree of risk to participants -continuing participants -continuing review from the review from the committee itself.committee itself.

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Finally.….Finally.….We now have:We now have: An understanding of what phase our trial is in An understanding of what phase our trial is in Approval for our studyApproval for our study Signed Consent documentSigned Consent document Ongoing protection right through our studyOngoing protection right through our study

RememberRememberThe The Research TeamResearch Team has to has to ensureensure that the that the

study is performed and the data are study is performed and the data are generated generated in compliancein compliance to GCP and the to GCP and the regulatory authorities.regulatory authorities.

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ReviewReview

The Nuremberg Code was the first ethical code to The Nuremberg Code was the first ethical code to provide us with some guidelines for “permissible medical provide us with some guidelines for “permissible medical experiments.”experiments.”

The Declaration of Helsinki provides additional guidelines The Declaration of Helsinki provides additional guidelines especially relating to physicians conducting research especially relating to physicians conducting research with therapeutic intent on patients.with therapeutic intent on patients.

The Tuskegee Study led to the development of the The Tuskegee Study led to the development of the Belmont Report.Belmont Report.

The three fundamental ethical principles that guide the The three fundamental ethical principles that guide the ethical conduct of research are Respect for Persons, ethical conduct of research are Respect for Persons, Beneficence and Justice.Beneficence and Justice.

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ReviewReview Research conduct is further guided by the ICH GCP Research conduct is further guided by the ICH GCP

and the CIOMS guidelines.and the CIOMS guidelines.

The ICH GCP was initially developed to guide the The ICH GCP was initially developed to guide the ethics and standards for drug development and ethics and standards for drug development and registration. registration.

The CIOMS guidelines focus on research conducted in The CIOMS guidelines focus on research conducted in developing countries by developed countries.developing countries by developed countries.

““Guidelines for Good Practice in the conduct of Clinical Guidelines for Good Practice in the conduct of Clinical

Trials in Human Participants in South Africa.” is the Trials in Human Participants in South Africa.” is the document that provides SA with clear standards of document that provides SA with clear standards of GCP and incorporates the above mentioned guidelines GCP and incorporates the above mentioned guidelines . .

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ReviewReview

There are specific guidelines that protects There are specific guidelines that protects Children, Adolescents and Vulnerable Children, Adolescents and Vulnerable communities even further and we must be communities even further and we must be aware of these guidelines.aware of these guidelines.

In clinical research, the commitment to In clinical research, the commitment to participants is to safeguard their interests participants is to safeguard their interests throughout the study. This can be done throughout the study. This can be done with ongoing informed consent, safety with ongoing informed consent, safety reporting, continuing IRB review and safety reporting, continuing IRB review and safety monitoring.monitoring.

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ReviewReview Every drug trial has to go through the following Every drug trial has to go through the following

Phases:Phases: Phase I: “Is the treatment safe ?”Phase I: “Is the treatment safe ?”

Phase II: “Can the treatment work ?”Phase II: “Can the treatment work ?”

Phase III: “Is the new treatment better than existing Phase III: “Is the new treatment better than existing treatment or placebo?”treatment or placebo?”

Phase IV: “Is there a better way to use this Phase IV: “Is there a better way to use this treatment ?”treatment ?”

The research team have to ensure that the research is The research team have to ensure that the research is performed and the data are generated in compliance performed and the data are generated in compliance to GCP and the regulatory authorities.to GCP and the regulatory authorities.

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Clinical Research Practice 2Clinical Research Practice 2

This presentation is produced by Aeras Global TB Vaccine FoundationSM in collaboration with the University of Cape Town and the South African Tuberculosis Vaccine Initiative.

A special thanks to Greg Hussey F.S.C.H., Tony Hawkridge, F.C.P.H.M., Hassan Mohammed, M. Med, Deon Minnies, Marie Buchanan, Hons.B.Soc.Sc, Marijke Geldenhuys, MSHS CRA, Sylvia Silver, D.A., Jen Page, M.Ed. for their contributions and support for this presentation.