Presentation on theme: "Overview of Good Clinical Practices (GCPs)"— Presentation transcript:
1 Overview of Good Clinical Practices (GCPs) Barbara Pennington, RN, MSPPD
2 Why Regulate Clinical Research? Ensure the rights, safety, and well-being of participantsScientific Integrity of data3
3 Good Clinical Practices (GCPs) Standards for designing, conducting, performing, monitoring, auditing, recording, analyzing, and reporting clinical trials.GCPs are not located in a single document - they are the collective body of knowledge that provide the industry standards, regulatory requirements, etc.5
4 GCP OHRP ICH 21 CFR 45 CFR 46 International FDA Electronic Docs. Inf. Consent$ DisclosureIRBsIND regs.IRBsInf. ConsentWomenPrisonersChildrenglossaryprinciplesIRBsInvestigatorSponsorEssential Docs
5 U.S. FDA (Food and Drug Administration) Branch of the United States Department of Health and Human ServicesRegulates all aspects of pharmaceutical industryTitle 21 of the Code of Federal Regulations (CFR)Note that complete listing of specific sections of 21 CFR are on next slide and on page B-15 of module10
6 CFR Title 21 Parts applicable to clinical research: Part 11 - Electronic Records and SignaturesPart 50 - Protection of Human SubjectsPart 54 - Financial Disclosure by Clinical InvestigatorsPart 56 - Institutional Review BoardsPart Investigational New Drug ApplicationPart Applications for FDA Approval to Market a New Drug or an Antibiotic DrugPart Biological ProductsPart Medical Devices11
7 Form FDA 1572 Contract between FDA and Investigator Logistics such as names and addressesSection 9Commitments of the Investigator
8 Investigator of Record (IOR) Agreement For Non-IND studiesIdentifies key personnel, facilities, labs, IRBsAlso lists the commitments of the investigator
9 Commitments of the IOR Comply with protocol Ensure compliance of IRB and consent process with 45CFR 46Report AEsAccurate record keeping and accessNo changes to study without permission of Sponsor and IRB
10 This is a Non-IND StudyDo we have to worry about FDA?
11 Office for Human Research Protections (OHRP) OHRP responsible for ensuring the safety and welfare of people who participate in HHS sponsored researchUnder the DHHS Assistant Secretary of Health45 CFR part 46Formerly OPRRThe HHS (Health and Human Services Department) now has oversight for OHRP, previously known as OPRR, where this department reported to NIH.
12 45 CFR part 46 IRB Informed Consent Protection of Fetuses, Pregnant WomenProtection of PrisonersProtection of ChildrenPer the Code of Federal Regulations (CFR), this policy applies to all research involving human subjects conducted, supported or otherwise subject to regulation by any Federal Department or Agency.This policy does not affect any State or local laws or regulations which may otherwise be applicable and which provide additional protections for human subjects. In other words, if the local regulations are more stringent, those additional local requirements will still apply. The same is true of foreign laws or regulations.
13 45CFR 46 Subpart A The “Common Rule” Protection of Human Subjects IRB/IECInformed ConsentVariations from FDA Regulations
14 45CFR 46 Subpart BProtections for Pregnant Women, Fetuses and NeonatesDefinitionsRecent revisions
15 45CFR 46 Subpart CAdditional Protections for Prisoners involved in researchDefinition of PrisonerAdditional IRB DutiesPermitted Research
16 45CFR 46 Subpart DAdditional Protections for Children involved in ResearchAssentMinimal risks
17 International Conference on Harmonisation (ICH) Guidelines for Good Clinical Practices
18 Objectives of ICH guidelines Provide a unified standardEU; US; JapanTo facilitate mutual acceptance of clinical dataDeveloped in accordance with existing standards in US, EU, Japan, Australia, Canada, Nordic Countries, and WHOThe ICH guidelines were an attempt on the part of the European Union, Japan and the US to standardize the practice of clinical trials. So if a pharmaceutical company in the US has gone through the rigors of taking a drug through the approval process in the US and they want to market the drug in Japan, they don’t have to reinvent the wheel, so to speak. The Japanese regulatory authorities will recognize that if ICH guidelines have been adhered to, then the product should be able to go through the approval process in Japan without having to perform phase I-III testing all over again.Several other countries recognize the ICH guidelines as a standard of clinical trials practice as well.
19 ICH GCP Consolidated Guideline E6 GlossaryPrinciples of ICH GCPInformation regarding:IRB/IECInvestigatorSponsorProtocolInvestigator’s BrochureEssential DocumentsHave class get out purple book and review Table of Contents on page 165.Note page 163 contains information regarding inclusion in Federal Register.12
20 Principles of ICH GCP Conduct trials according to GCP Weigh risks vs. benefitsProtect the subjectsHave adequate information to justify trialWrite a sound protocolReceive IRB/IEC approvalUse qualified physiciansEncourage participants to look for the inclusion of these principles as they work through modules.13
21 Principles of ICH GCP Use qualified support staff Obtain informed consentRecord information appropriatelyProtect confidentialityHandle investigational products appropriatelyImplement quality systems14
22 Local RegulationsMay have more detailed regulations that apply locallyDo not conflict with national regulations15
23 Sponsor Policies US Department of Health and Human Services NIH/DAIT/DAIDSEssential Document and Source Document SOP
24 Internal SOPs Standard Operating Procedures (SOPs) Detailed instructions describing the what, when, where, and by whom of performing an activity18
27 Investigator Responsibilities* Investigator Qualifications and Agreementsqualified by education, training and experiencefamiliar with protocol, IB, IPaware of and compliant with GCPs and applicable regspermit monitoringlist of qualified personnel who are delegated duties*(ICH 4.1-9)These next few slides are taken from the ICH guidelines, chapter 4 which is all about the Investigator’s responsibilities. Investigator’s are required to ensure that the research staff (Subs, coordinators, data entry personnel) are qualified by education, training and experience to perform their study specific duties.The delegation of duties list (noting study personnel and outlining each individuals’ responsibility) must be kept current throughout the duration of the study.
29 Investigator Responsibilities* Adequate Resourcesrecruit adequate subjectssufficient timequalified staff and adequate facilitiesMedical Care of Subjectsresponsible for all trial related medical decisions*(ICH )There should also be documentation that notes site personnel have been informed and adequately trained to perform their research related responsibilities and that they understand their study specific duties.Monitors will inspect the facilities at the research site at periodic intervals to ensure that the facilities and staff remain adequate to conduct the research.
30 Investigator Responsibilities* Communication with IRBapprovalsensure complianceCompliance with ProtocolInvestigational Product (IP)proper delegation of duties*(ICH )This is something the FDA is really cracking down on lately as I’m sure you’ve heard about the recent problems with IRBs at institutions such as Duke, UAB, U of Colorado, and certainly the big issues with genetics studies at U Penn. IRB/ investigator relations problems have brought this issue to the headlines and therefore, have been and will continue to be more carefully scrutinized in the future by regulatory authorities.The system of checks and balances as set forth in the CFR and ICH requires that the PI be responsible for ensuring that his/her local IRB is compliant with CFR part 56, which outlines the guidelines for IRBs.
31 How can the PI be held responsible for what the IRB does or does not do? Document ALL interaction (verbal, electronic, written) with IRB including reminders of upcoming review requirements
32 Investigator Responsibilities* Regulations require IRB is aware of changes in research activity“…OHRP finds that changes to research protocol were implemented by investigators without IRB approval…”
33 Investigator Responsibilities* Randomization & UnblindingInformed ConsentRecords and Reportsensure accuracy, completeness, legibility and timeliness of datadata on CRF derived from Source Documentschanges made appropriatelyallow direct access*(ICH )The PI is responsible for making sure that randomization codes remain secure and intact. The PI also ensures that records, whether regulatory documents, source documents or CRFs are legible and, if there are corrections, deletions, additions or any changes, that these are authorized by the PI.
34 Regulatory Authorities will inquire about: Source of study subjectsDid they have the disease under studyDid they meet inclusion/exclusion criteriaWas the protocol precisely followedWere AEs reported appropriately
35 Common OHRP FindingsIRB failed to review the research at a convened meetingfailure to review grant applicationsInvestigators failed to promptly report unanticipated problems involving risks to subjects to IRB, OHRP and Sponsor
36 Common OHRP FindingsContinuing review of research was NOT substantive nor meaningfulinclude a summary of AEs and unanticipated problems# of subjects accruedsummary of recent literature, findings amendments, modifications since last reviewrelevant reports, informationcurrent consent form
37 Common OHRP FindingsIRB did not ensure additional protections for vulnerable subjectsIRB members with conflicting interest participated in reviewIRB meeting convened without Quorum (Non-scientist absent)
38 Common OHRP Findings IRB review of NIH approved consent any changes to the sample consent form related to risks or alternative procedures must be justified in writing by the investigator, approved by IRB and reflected in the IRB minutes
39 OHRP Finds that the IRB: Lacks diversityis overburdened by large volumelevel of staff support is insufficientmembers lack detailed understanding of regs. for protection of human subjectsinadequate procedures for reporting of unanticipated problems
40 We Applaud COMPLIANCE GCPs Protocol DAIT/DAIDS procedures Local regulationsRemember, if you are compliant with GCPs, the protocol, DAIDS procedural guidelines and your local state/country and IRB regulations, you will be “audit proof”.