The Fundamentals of International The Fundamentals of International Clinical ResearchClinical Research

ICH and GOOD CLINICAL PRACTICESICH and GOOD CLINICAL PRACTICESLila SchweinsLila Schweins

Family Health InternationalFamily Health International

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General questionsGeneral questions……

What is ICH?What is ICH? What does it do?What does it do?What is GCP?What is GCP? What is it for?What is it for?

Why should we implement GCP?Why should we implement GCP?

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ICHICHInternational Conference on HarmonizationInternational Conference on Harmonization

GCPGCPGood Clinical PracticesGood Clinical Practices

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ICH HistoryICH History

Background:Background:Drug development Drug development globalglobal, , Regulation Regulation nationalnational

Purpose:Purpose:to harmonize very detailed to harmonize very detailed technical requirementstechnical requirements

Participants:Participants:Regulatory agencies/ industry fromRegulatory agencies/ industry fromEU, Japan, USEU, Japan, US

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ICH HistoryICH History

Concerns:Concerns:–– Rising costs of health careRising costs of health care–– Increasing costs of R+DIncreasing costs of R+D–– Public expectation of little delay for Public expectation of little delay for

new, safe, efficacious new, safe, efficacious txtx

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ICH GoalICH Goal

Remove redundancy / duplication in Remove redundancy / duplication in development and review processdevelopment and review processFor new medicinal products, single set of For new medicinal products, single set of data should demonstrate:data should demonstrate:–– SafetySafety

–– QualityQuality

–– EfficacyEfficacy

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ICH ProcessesICH Processes

ICH members develop ICH members develop guidelinesguidelinesthrough stepthrough step--wise processwise processApplicable to:Applicable to:–– DrugsDrugs–– BiologicsBiologics–– Medical devices (test articles)Medical devices (test articles)

Approved by ICH members, Approved by ICH members, then adopted by National Regulatory then adopted by National Regulatory AuthoritiesAuthorities

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ICH TopicsICH Topics

Safety [S] Safety [S] -- in vitroin vitro & & in vivoin vivo preclinical testing preclinical testing

Quality [Q] Quality [Q] -- chemical & pharmaceutical QAchemical & pharmaceutical QA

Efficacy [E] Efficacy [E] -- clinical studies in humansclinical studies in humans

Multidisciplinary [M] Multidisciplinary [M] -- terminologyterminology

-- electronic standards electronic standards -- common documentscommon documents

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ICH ICH EfficacyEfficacy GuidelinesGuidelines

E1: Exposure E1: Exposure (to assess clinical safety)(to assess clinical safety)

E2: Clinical Safety E2: Clinical Safety (includes data management)(includes data management)

E3: Study Reports E3: Study Reports E4: Dose Response StudiesE4: Dose Response Studies

E5: Ethnic Factors E5: Ethnic Factors (acceptability of foreign data)(acceptability of foreign data)

E6: Good Clinical Practices (GCP)E6: Good Clinical Practices (GCP)E7/11: Special Populations E7/11: Special Populations E8/9/10: Clinical Trials Design (E8/9/10: Clinical Trials Design (includes biostatisticsincludes biostatistics))E12: Therapeutic CategoriesE12: Therapeutic Categories

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ICH ICH Good Clinical PracticesGood Clinical Practices (GCP)(GCP)

Accepted for Accepted for generating clinical generating clinical trial data intended for trial data intended for submission to submission to regulatory agenciesregulatory agencies

Consist of:Consist of:–– Guiding PrinciplesGuiding Principles–– StandardsStandards–– RequirementsRequirements

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ICH GCPICH GCP

Principles can apply to other Principles can apply to other clinical research: clinical research:

–– NIH Guidance on conduct of clinical researchNIH Guidance on conduct of clinical research–– NIAID Clinical Terms of Award NIAID Clinical Terms of Award

Governs all clinical research supported Governs all clinical research supported by extramural funds by extramural funds

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ICH GCPICH GCPSSTANDARDSTANDARDS

International ethical and International ethical and scientific quality standard for:scientific quality standard for:

DesigningDesigning

ConductingConducting

RecordingRecording

ReportingReporting

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GCP GCP DesignDesign StandardsStandardsProtocol, Investigator Brochure contentProtocol, Investigator Brochure contentScientifically sound, feasibleScientifically sound, feasibleAdequate resourcesAdequate resourcesRandomization / blinding proceduresRandomization / blinding procedures

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GCP GCP ConductConduct StandardsStandardsRegulatory + IRB approvalsRegulatory + IRB approvalsComply with protocolComply with protocolInformed consent, ConfidentialityInformed consent, ConfidentialityMedical management, adverse eventsMedical management, adverse eventsProduct accountabilityProduct accountabilityQualifications + TrainingQualifications + Training

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GCP GCP RecordingRecording StandardsStandards

CRF completionCRF completionData handling Data handling Security, audit trailsSecurity, audit trailsProduct Product AccountabilityAccountabilityStudy Files/ Essential Study Files/ Essential DocumentsDocuments

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GCPGCP ReportingReporting StandardsStandards

Adverse Events, interim reviews, Adverse Events, interim reviews, progress reports, final reports, progress reports, final reports, monitoring/audit reports to: monitoring/audit reports to: –– SponsorsSponsors–– IRB/IECIRB/IEC–– Regulatory authoritiesRegulatory authorities–– Other investigatorsOther investigators

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ICH GCPICH GCPREQUIREMENTSREQUIREMENTS

Requirements & responsibilities Requirements & responsibilities delineated for:delineated for:–– IRB/IEC IRB/IEC

–– Investigators Investigators

–– SponsorsSponsors

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IRB/IEC Requirements & IRB/IEC Requirements & ResponsibilitiesResponsibilities

–– ResponsibilitiesResponsibilities–– Composition, function, operationsComposition, function, operations–– ProceduresProcedures–– RecordsRecords

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Investigators Requirements (1):Investigators Requirements (1):

–– Professional qualifications and agreementsProfessional qualifications and agreements–– Adequate resourcesAdequate resources–– Medical care of trial subjectsMedical care of trial subjects–– IRB communicationIRB communication–– Protocol complianceProtocol compliance–– Investigational productInvestigational product

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Investigators Requirements (2):Investigators Requirements (2):

–– Randomization + Randomization + unblindingunblinding–– Informed consent of trial subjectsInformed consent of trial subjects–– Records + reportsRecords + reports–– Study conductStudy conduct

Safety reportingSafety reportingPremature trial termination or suspensionPremature trial termination or suspension

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GCP Essential Documents: GCP Essential Documents: Permit evaluation of trial Permit evaluation of trial conduct and data qualityconduct and data quality

Files ofFiles of–– InvestigatorInvestigator–– Sponsor Sponsor

Phase of trial:Phase of trial:–– Before startBefore start–– During conduct During conduct –– After completionAfter completion

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ComplianceCompliance with GCPwith GCP provides provides public assurance of:public assurance of:

Protection of Protection of subjectsubject’’s rights, s rights, safety, wellsafety, well--being being Consistence with Consistence with Helsinki DeclarationHelsinki DeclarationCredible DataCredible Data

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SUMMARYSUMMARY

ICHICH = International Conference on = International Conference on HarmonizationHarmonization

–– ICH sets international standards for ICH sets international standards for technical requirements to license technical requirements to license new drugsnew drugs

–– Issues guidelines Issues guidelines –– DMID follows ICH guidelines DMID follows ICH guidelines for clinical

research conduct and oversight

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SUMMARYSUMMARY

GCPGCP = Good Clinical Practices (ICH E6)= Good Clinical Practices (ICH E6)

–– Covers design, conduct, recording and Covers design, conduct, recording and reporting of clinical research reporting of clinical research

–– Designed to ensure:Designed to ensure:

Ethical research, Ethical research,

High quality, credible dataHigh quality, credible data

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Web resources for ICH/GCPWeb resources for ICH/GCP

US FDA: US FDA: http://http://www.fda.gov/oc/ohawww.fda.gov/oc/oha

ICH Website: ICH Website: http://www.ifpma.org/ich1.htmlhttp://www.ifpma.org/ich1.html