© 2004 Aeras Global TB Vaccine Foundation Introduction to Clinical Research Clinical Research Practice 1

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

Introduction to Clinical Introduction to Clinical ResearchResearch

Clinical Research Clinical Research Practice 1Practice 1

22 22© 2004 Aeras Global TB Vaccine Foundation© 2004 Aeras Global TB Vaccine Foundation

The basics of clinical research, types of The basics of clinical research, types of clinical trials and why clinical research is clinical trials and why clinical research is necessary.necessary.

Good Clinical Practice and Good Laboratory Good Clinical Practice and Good Laboratory Practice that guide the conduct of clinical Practice that guide the conduct of clinical research.research.

The importance of protecting participants and The importance of protecting participants and the informed consent procedures.the informed consent procedures.

The overall goals of the current trials.The overall goals of the current trials.

This Course Will Introduce You This Course Will Introduce You To:To:


Objectives:Objectives: Define clinical research and explain why Define clinical research and explain why

we perform clinical research.we perform clinical research. Define Standard Operating Procedure.Define Standard Operating Procedure. Identify the types of clinical research trials.Identify the types of clinical research trials. Define protocol.Define protocol. State the protections given to human State the protections given to human

participants in clinical research.participants in clinical research. Define Good Clinical Practice and Good Define Good Clinical Practice and Good

Laboratory Practice.Laboratory Practice.


Objectives:Objectives: Explain why GCP and training given by the Explain why GCP and training given by the

PDP are important to you.PDP are important to you. Identify staff that must comply to research Identify staff that must comply to research

ethics and standards. ethics and standards. Explain the importance of “amendments” Explain the importance of “amendments”

to a protocol.to a protocol. Define Case Report Forms and Source Define Case Report Forms and Source

documents and their importance in a trial.documents and their importance in a trial. Define informed consent and list some of Define informed consent and list some of

the rules of the process.the rules of the process. State the overall goals of the clinical trial State the overall goals of the clinical trial

you are working on.you are working on.


What Is Clinical Research?What Is Clinical Research?

A scientific research study.A scientific research study. A clinical trial looking for answers to A clinical trial looking for answers to

specific questions.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.


So……So……

Clinical Research Is… Clinical Research Is…

Research performed on humans.Research performed on humans.

Designed to answer specific Designed to answer specific questions related to human disease, questions related to human disease, diagnosis, prevention, outcomes and diagnosis, prevention, outcomes and treatments.treatments.


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.


What Happens In a Clinical What Happens In a Clinical Trial?Trial?

Human participants are recruited for a Human participants are recruited for a particular study based on stated criteria as particular study based on stated criteria as described in the protocol of the study.described in the protocol of the study.


Then…….Then…….

Participants are fully informed about the Participants are fully informed about the trial and give informed consent to trial and give informed consent to participate in the clinical trial.participate in the clinical trial.

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© 2004 Aeras Global TB Vaccine Foundation© 2004 Aeras Global TB Vaccine Foundation

And Only Then….And Only Then….

A team of doctors, nurses and other research A team of doctors, nurses and other research professionals:professionals: check the health of the participant at the check the health of the participant at the

beginning of the trial.beginning of the trial. give specific instructions for participating in the give specific instructions for participating in the

trial.trial. monitor the participant carefully during the trial.monitor the participant carefully during the trial. collect the relevant datacollect the relevant data analyze the data and draw conclusions analyze the data and draw conclusions report results and share conclusionsreport results and share conclusions

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How Does The Team Ensure How Does The Team Ensure Uniformity In Research?Uniformity In Research?

Standard Operating Standard Operating ProceduresProcedures

Detailed, written Detailed, written instructions to instructions to achieveachieveuniformity of the uniformity of the performance of a performance of a specific function.specific function.

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Types of Clinical Research Types of Clinical Research TrialsTrials

Treatment trialsTreatment trials Prevention trialsPrevention trials Diagnostic trialsDiagnostic trials Screening trialsScreening trials Quality of life trialsQuality of life trials

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Types of Clinical Research Types of Clinical Research TrialsTrials

Treatment trials:Treatment trials: Test new treatments, new Test new treatments, new combinations of drugs, or new combinations of drugs, or new approaches to surgery or radiation approaches to surgery or radiation therapy.therapy.

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Prevention trials:Prevention trials: Look for better ways to prevent disease in Look for better ways to prevent disease in people who have never had the disease people who have never had the disease or to prevent a disease from returning. or to prevent a disease from returning. May include medicines, vitamins, May include medicines, vitamins, vaccines, minerals, or lifestyle changes.vaccines, minerals, or lifestyle changes.

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Diagnostic trials: Diagnostic trials: Are conducted to find better tests or Are conducted to find better tests or procedures for diagnosing a procedures for diagnosing a particular disease or condition.particular disease or condition.

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Screening trials:Screening trials: Test better ways to detect a disease Test better ways to detect a disease or particular health condition.or particular health condition.

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Quality of life trials: Quality of life trials: Explore ways to improve comfort and Explore ways to improve comfort and the quality of life for individuals with the quality of life for individuals with a chronic illness.a chronic illness.

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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

ResearcResearchh

Analyse Analyse ResultsResults

Report Report ResultsResults

Get RegulatoryGet Regulatory

ApprovalApproval

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Key Parts of the ProcessKey Parts of the Process Find Funding:Find Funding:

A A sponsorsponsor, , pharmaceutical pharmaceutical company, research company, research institution, or other institution, or other organization funds the organization funds the project. project.

Protocol:Protocol: The study plan. Written The study plan. Written procedures detailing the procedures detailing the steps to conduct a study, steps to conduct a study, keep participants safe keep participants safe and ensure valid data. and ensure valid data.

Get Regulatory Get Regulatory Approval:Approval: Regulatory bodies Regulatory bodies monitor and approve monitor and approve research.research.

Institutional Review Institutional Review Board or Ethics Board or Ethics Committee (IRB/IEC)Committee (IRB/IEC)

Medicines Control Medicines Control Council (MCC)Council (MCC)

South African South African National Accreditation National Accreditation System (SANAS)System (SANAS)

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Performing Research in South Performing Research in South Africa Africa Offers an Unique Offers an Unique

Environment Environment

SouthAfrica

High technological medical

expertise and infrastructure.

Significant burden of disease.

Racial-CulturalDiversity

Money, resources and other support for research.

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Rapid Increase in ResearchRapid Increase in Research

South Africa has seen a 40% growth in South Africa has seen a 40% growth in research since 1997.research since 1997.

Could lead to the potential for Could lead to the potential for unscrupulous, unethical and unscrupulous, unethical and unnecessary conduct of clinical unnecessary conduct of clinical research. research.

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Risk of Research MisconductRisk of Research MisconductGreatest When Dealing With…Greatest When Dealing With…

Poor populations.Poor populations. Low levels of literacy.Low levels of literacy. Unquestioning acceptance of Unquestioning acceptance of

authority.authority. Great need for health services.Great need for health services. No knowledge of research.No knowledge of research.

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Research Is So “New” …Can Research Is So “New” …Can You See Why We Need You See Why We Need

Guidelines?Guidelines?In the light of this growth and unique environments, the need to carefully regulate and guide the conduct of clinical trials becomes urgent and necessary.

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HowHow Do We Protect Our Research Do We Protect Our Research Participants Against Research Participants Against Research

Misconduct?Misconduct?

Research principles and guidelinesResearch principles and guidelines

Research regulationsResearch regulations

Informed ConsentInformed Consent

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Principles to Protect Principles to Protect 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 rules by which GCP is the rules by which we conduct our research.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 framework within which laboratory studies are planned, performed, monitored, are planned, performed, monitored, recorded, reported and archived.recorded, reported and archived.

Simply put …. Simply put …. GLP is the rules of research in the GLP is the rules of research in the lab.lab.

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GCPGCP

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History of GCPHistory of GCP

Nazi Medical War Nazi Medical War Crimes Crimes

Nuremberg Code - 1947

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DeclarationDeclaration of Helsinki (DOH) of Helsinki (DOH) 19641964

Developed by the World Medical Association

First significant effort of the medical community to regulate itself.

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Tuskegee Syphilis Study 1932-Tuskegee Syphilis Study 1932-19721972

Belmont Report 1979

Cornerstone for ethical principles underlying the acceptable conduct of

research using human volunteers.

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Many regulations……needed one Many regulations……needed one standard standard

International Conference on Harmonization

April 1990

Principles of ICH GCPPrinciples of ICH GCP

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13 Principles of ICH GCP13 Principles of ICH GCP

Two important principles are:Two important principles are:

The rights, safety, and well-being of the The rights, safety, and well-being of the trial participants are the most important trial participants are the most important considerations and should prevail over considerations and should prevail over the interest of science and society.the interest of science and society.

Each individual involved in conducting a Each individual involved in conducting a trial should be qualified by education, trial should be qualified by education, training, and experience to perform his training, and experience to perform his or her respective task(s).or her respective task(s).

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GLPGLP

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History of GLPHistory of GLP

Malpractice – 1970’sMalpractice – 1970’s Organization for Economic Co-Organization for Economic Co-

operation and Development (OECD)operation and Development (OECD)

30 Countries-1981

OECD GLP PrinciplesOECD GLP Principles

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OECD GLP Principles

Regulates the practices of scientists Regulates the practices of scientists working on the safety testing of working on the safety testing of prospective drugs.prospective drugs.

Imposed by regulatory authorities.Imposed by regulatory authorities.

South African National Accreditation South African National Accreditation System (SANAS)System (SANAS)

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GLP: Fundamental PointsGLP: Fundamental Points

ResourcesResources

RulesRules

CharacterizationCharacterization

DocumentationDocumentation

Quality AssuranceQuality AssurancePhoto courtesy of Aeras Global TB Vaccine Foundation.

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

As part of the research team, each As part of the research team, each and every one of us is responsible for and every one of us is responsible for following ethical guidelines and following ethical guidelines and ensuring valid and credible results.ensuring valid and credible results.

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How Is Research How Is Research Regulated?Regulated?

ResearchParticipant

InstitutionalInstitutional

Review BoardReview Boardor Ethicsor Ethics

Committee Committee

MedicinesMedicinesControl CouncilControl Council

Data SafetyData SafetyMonitoringMonitoring

Board Board

SANASSANAS

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…………What If We Need To What If We Need To Change Something ?Change Something ?

Remember the Protocol?......Remember the Protocol?......

Ask for a Ask for a protocol amendment……protocol amendment……

““A written description of a change(s) to A written description of a change(s) to or formal clarification of a protocol.”or formal clarification of a protocol.”

( Definition from the ICH Guideline for Good Clinical ( Definition from the ICH Guideline for Good Clinical Practice 1.45)Practice 1.45)

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Data CollectionData CollectionSource DataSource Data All information in original records and certified copies All information in original records and certified copies

of original records of clinical findings, observations, of original records of clinical findings, observations, or other activities in a clinical trial necessary for the or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. (ICH 1.51)reconstruction and evaluation of the trial. (ICH 1.51)

Source DocumentsSource Documents Original documents, data and records. (ICH 1.52)Original documents, data and records. (ICH 1.52)

Case Report Form (CRF)Case Report Form (CRF) A printed, optical, or electronic document designed A printed, optical, or electronic document designed

to record all of the protocol required information to to record all of the protocol required information to be reported to the sponsor on each trial subject. (ICH be reported to the sponsor on each trial subject. (ICH 1.11)1.11)

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A Few Rules for Completing A Few Rules for Completing Study Documentation:Study Documentation:

Make sure that you are designated to Make sure that you are designated to complete the documents.complete the documents.

Write legibly.Write legibly. Do not leave any blank fields on documents.Do not leave any blank fields on documents. Do not use correctional fluid.Do not use correctional fluid. Double check that information is accurate Double check that information is accurate

and consistent with the source document.and consistent with the source document. Make corrections and edits according to Make corrections and edits according to

GCP guidelines. GCP guidelines.

(ICH 4.9)(ICH 4.9)

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Informed ConsentInformed Consent A process by which a subject A process by which a subject voluntarily confirmsvoluntarily confirms

his or her his or her willingnesswillingness to participateto participate in a particular in a particular trial,trial, ……afterafter having been informed of having been informed of all aspectsall aspects of the of the

trial trial ……that are that are relevantrelevant to the subject’s decision to to the subject’s decision to

participate.participate.

Informed consent is documented by means of a Informed consent is documented by means of a written, signed and dated informed consent form.written, signed and dated informed consent form. (ICH 1.28) (ICH 1.28)

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According to the ICH GCP Guidelines According to the ICH GCP Guidelines 4.8.5..4.8.5..

““The The investigatorinvestigator, or a , or a person person designateddesignated by the investigator, by the investigator, should fully inform the should fully inform the participant/legal representative, of all participant/legal representative, of all pertinent aspects of the trial……”pertinent aspects of the trial……”

Who Is Responsible For Who Is Responsible For Performing The Informed Performing The Informed

Consent Procedure?Consent Procedure?

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The Rules Of The Informed The Rules Of The Informed Consent ProcessConsent Process

ICH GCP GUIDELINESICH GCP GUIDELINES4.84.8

(see attached handout)(see attached handout)

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No study procedures are allowed No study procedures are allowed

before the informed consentbefore the informed consent

process is complete and theprocess is complete and the

informed consent document is informed consent document is

signedsigned..

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? Projects/Trials ?? Projects/Trials ?

? OBJECTIVES ?

CCS

Adoll.

BCG HIV

BCG RCT

PHASE I

TB HIV Neo-

natal

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Other Relevant Definitions To Other Relevant Definitions To Make The Protocol a Little Make The Protocol a Little

Clearer:Clearer: Study Population:Study Population: Entire group of Entire group of

individuals that has common individuals that has common characteristics designated by the characteristics designated by the researcher.researcher.

Inclusion/Exclusion criteria: Inclusion/Exclusion criteria: The The medical or social standards determining medical or social standards determining whether a person may or may not be whether a person may or may not be allowed to enter a clinical trial.allowed to enter a clinical trial.

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Using Your Current Study Using Your Current Study Protocol:Protocol:

Find the Following and Find the Following and Explain…….Explain…….

Study titleStudy title Primary Primary

objectivesobjectives Secondary Secondary

objectivesobjectives

Study populationStudy population Inclusion criteriaInclusion criteria Exclusion criteriaExclusion criteria

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ReviewReview Clinical research is performed on human Clinical research is performed on human

volunteers and is used to answer specific volunteers and is used to answer specific questions with the ultimate goal of improving questions with the ultimate goal of improving human health.human health.

The research team follows SOP’s to ensure The research team follows SOP’s to ensure uniformity within a research study.uniformity within a research study.

There are 5 types of clinical research trials.There are 5 types of clinical research trials.

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ReviewReview The protocol is the study plan. If we would want to The protocol is the study plan. If we would want to

change anything in this plan we need to amend it change anything in this plan we need to amend it by using the correct process.by using the correct process.

Compliance with GCP and GLP ensures valid Compliance with GCP and GLP ensures valid research data and protects the participants against research data and protects the participants against research misconduct.research misconduct.

Research is regulated by various committees and Research is regulated by various committees and regulatory bodies to ensure compliance with ethics regulatory bodies to ensure compliance with ethics and standards.and standards.

Data collection is an important part of the research Data collection is an important part of the research process. Data is captured on specified CRF’s.process. Data is captured on specified CRF’s.

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ReviewReview Proper completion of study documentation is critical Proper completion of study documentation is critical

to compliance with GCP and GLP. It also helps to compliance with GCP and GLP. It also helps ensures valid study results.ensures valid study results.

The informed consent process, where participants The informed consent process, where participants are fully informed about details of the study, is key are fully informed about details of the study, is key to protecting the rights of research participants. to protecting the rights of research participants.

No study procedures are allowed to happen before No study procedures are allowed to happen before the informed consent documents have been signed.the informed consent documents have been signed.

Each clinical research trial has a unique goal. It is Each clinical research trial has a unique goal. It is important for you to understand the goal of the trial important for you to understand the goal of the trial you are working on, so you can best support the you are working on, so you can best support the trial goals in your routine work.trial goals in your routine work.

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Clinical Research Practice 1Clinical Research Practice 1

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 Professor Greg Hussey, Dr. Tony Hawkridge, MBChB, Deon Minnies, Lucrecia Michaels, Marie Buchanan, Marijke Geldenhuys, MSHS CRA, Dr. Sylvia Silver, D.A., and Jen Page, M.Ed. for their contributions and support for this presentation.