V4.0 2013-02-28

NIDCR National Institute of Dental and Craniofacial ResearchNational Institutes of HealthCROMS Clinical Research Operations and

Management SupportRho, Inc., Federal Division

Clinical Research Responsibilities for

NIDCR-Funded Investigators

Note that this is a general slide presentation designed for a broad audience of clinical researchers.

Accordingly, some sections may not apply to your protocol. Information that may not be applicable for all studies is

indicated via blue italics.

Disclaimer

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Examples include references to:◦ Investigational Product (IP), the Investigator’s Brochure (IB),

or a study pharmacist◦ Safety reporting and adverse events◦ Randomization and unblinding procedures◦ Regulatory authorities◦ Clinical treatment (for a behavioral or study or a registry)

Disclaimer

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Good Clinical Practice (GCP) Guidelines (ICH-E6)◦ Widely accepted international research standards

Title 45 Code of Federal Regulations (CFR) Part 46 ◦ Applies to federally funded research◦ Federal regulations to protect human subjects◦ Subpart A: The Common Rule◦ IRB roles and responsibilities/Informed Consent

Basis for Research Roles and Responsibilities

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NIDCR Study Types

Clinical Trials involving a biomedical or behavioral intervention

Clinical Research Studies, including:◦ Observational◦ Specimen Collection◦ Epidemiology or Surveillance studies

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ObjectivesTo review key roles and responsibilities of investigators and staff engaged in NIDCR-funded research Human Subject Protection Administrative and Regulatory Responsibilities Research Planning and Considerations Documentation and Record Keeping

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Human Subject Protection:IRBs and the Informed Consent Process

The Institutional Review Board or Ethics Committee

Required for human subjects research supported by DHHS

Must register IRB with OHRP/File FWA Applications can be submitted online Commitment to comply with 45 CFR Part 46

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IRB Requirements Membership, functions, and operations Initial and continuing review of research Criteria for approval of research Decisions regarding termination/suspension of

study due to harm or noncompliance Documentation and record keeping

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IRB and Investigator Interactions Know your IRB’s review schedule and process Obtain/document IRB approval prior to initiating

research Obtain/document IRB approval prior to

implementing any protocol amendments (administrative or otherwise)

Notify IRB regarding adverse events (AEs) and unanticipated problems (UPs) as required

Obtain and document IRB acknowledgement of study completion

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The Consent Process Obtain without coercion or undue influence Language understood by subjects Cannot contain language waiving subject’s legal

rights Cannot release institution from liability for

negligence Answer questions/allow time for consideration Subjects must receive signed/dated copy of the

consent document

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Elements of Consent Document Statement that the study involves research Statement that participation is voluntary Information about purpose, duration, and

procedures Number of subjects involved in the study Description of risks, benefits, and alternatives Information about compensation/care for injury Statement regarding confidentiality of records

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Description of possible unforeseen risks Circumstances for termination without subject

consent Consequences of withdrawing from the study Additional costs that may result from participation Statement that new research findings will be shared Contact information for questions/concerns

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Elements of Consent Document (continued)

Special Provisions for Vulnerable Populations Title 45 CFR Part 46; Subparts B, C, and D

◦ Subpart B: Additional protections for pregnant women, human fetuses, and neonates

◦ Subpart C: Additional protections for prisoners◦ Subpart D: Additional protections for children

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Administrative and Regulatory Responsibilities

Administrative and Regulatory ResponsibilitiesInvestigators who are responsible for study conduct should: Have appropriate education, experience, and training Maintain current CV and credentials Thoroughly understand and comply with the protocol Comply with applicable regulations/GCP guidelines Follow your institution’s HIPAA requirement policies Permit monitoring by sponsors and their representatives

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Administrative and Regulatory Responsibilities (continued) Provide and document protocol, GCP/regulatory training Maintain a delegation of responsibilities log Maintain training records/log Maintain screening and enrollment logs Maintain subject code list Maintain monitoring visit log Create and maintain an investigator binder to store

documentation and records

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Research Planning and Considerations

Research Study PlanningWhen designing and developing a study protocol, consider: Time needed for the development of:

◦ the protocol and consent document ◦ additional documents such as the Manual of Procedures

and Case Report Forms/Data Collection Tools Recruitment and enrollment strategies for study

population Necessary time commitments for all investigators

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Research Study Planning (continued) Adequate ancillary staff support Proper training of research staff Available facilities and space Time required for review of these items by NIDCR

and the IRB

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Protocol Adherence Document investigators’ agreement to follow the

protocol◦ NIDCR protocol template has sign-off page

Adhere to the IRB-approved protocol/protocol amendments

Only deviate from the protocol to avoid immediate hazards to subjects

Document and report all protocol deviations to the IRB

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Adverse Event (AE) Reporting Review protocol for reporting requirements Notify subjects of care needed and provide referral Actively monitor, ensure care for, and document AEs Follow to resolution Report AEs to the IRB/Safety Committee and comply

with any specific guidance

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Unanticipated Problem (UP) Reporting Review protocol for reporting requirements Train study team members on UP definition Report UPs to the IRB/other oversight bodies

specified by the protocol, and comply with any specific guidance

Actively monitor, ensure care for, and document UPs Follow to resolution

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Documentation and Record Keeping

Adequate Documentation, Record Keeping, and Retention Permits evaluation of the conduct of a study Permits evaluation of data collected Demonstrates GCP and compliance with applicable

regulatory requirements Facilitates study management and oversight Allows for monitoring and evaluation of practices

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Documentation:Types of Essential Documents IRB-approved protocols, consents, advertisements IRB correspondence/approval letters CVs/credentials for investigators Staff training logs/records Delegation of Responsibilities log Screening/enrollment logs Subject ID code lists Signed consent documents and data collection forms Monitoring visit log/visit reports

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Monitoring The Clinical Site Monitoring Plan will include:

◦ Site Assessment◦ Site Initiation Meeting◦ Interim Monitoring Visits◦ Close-out Visit

Other monitoring may include:◦ Core lab◦ Data Coordinating Center / Data Management Center

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Data Collection and Management Describe how data will be collected and maintained

◦ Development of a Data Management Plan◦ Development of a source document management process

Develop Case Report Forms (CRFs) or appropriate data collection tools

Maintain source documentation Record data on study forms in a timely manner

◦ Examples include interview forms, questionnaires, data collection forms, research chart (paper or electronic format)

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Data Collection and Management (continued)

Ensure data is accurate, complete and legible Data corrections should not obscure original entries Implement data quality control procedures

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Specimens Includes (but is not limited to) collection, labeling,

processing, storage, shipment, and tracking of specimens

Handling in accordance with the requirements of the protocol, MOP, IRB, and applicable regulations

Tracking of final disposition of samples at end of study

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In Summary 45 CFR 46 & ICH E6 GCP Provides Guidance and

Standards for:◦ Rights, safety, and well-being of subjects◦ Roles and Responsibilities of Investigators and Research

Staff◦ Study conduct and protocol management◦ Safety reporting ◦ Documentation and Record Keeping

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Questions?

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Objective Resource

Protection of human subjects 45 CFR 46

Staff qualifications/training ICH E6, Sec 4.1. Sec 4.2

Research resources ICH E6, Sec 4.2

Protocol adherence ICH E6, Sec 4.5

Record keeping ICH E6, Sec 4.4.1, Sec 4.9, Sec 8

FAQs (OHRP Investigator Responsibilities)

http://answers.hhs.gov/ohrp/categories/1567

Resources

NIDCR ResourcesForms NIDCR Investigator of Record Agreement Delegation of Responsibilities Log Training Log Site Screening and Enrollment Log Subject Code List Adverse Event Forms Monitoring Visit Log

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NIDCR Resources (Continued)Training Presentations Investigator Responsibilities (ICH & GCP)

These resources and other tools are available through NIDCR’s Toolkit for Clinical Researchers:

http://nidcr.nih.gov/research/toolkit

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