socra review: investigator roles and responsibilities in clinical research john naim, phd director...

SoCRA Review: Investigator Roles and Responsibilities in Clinical Research

John Naim, PhDDirector

Clinical Trials Research UnitWest Virginia University

March 20, 2015

West Virginia Clinical and Translational Science Institute

Outline

• Historical Perspective• Legal Framework• Clinical Investigator• Roles and Responsibilities• GCP Q & A• Discussion

West Virginia Clinical and Translational Science Institute

Disclaimer

Information from: FDA Clinical Investigator Training Coursehttp://www.fda.gov/downloads/Training/ClinicalInvestigatorTrainingCourse/UCM378565.pdf

GCP questions from Paul Below presentation:http://www.slideshare.net/PaulBelow/so-you-think-you-know-gcp-mar-2013

West Virginia Clinical and Translational Science Institute

Historical Perspective

Past transgressions lead to the need for laws that protect the rights and welfare of human subjects.• Nuremberg Doctors Trial of 1946 (Nuremberg

Code)• Thalidomide Tragedy (Kefauver-Harris Amendment)• Tuskegee Experiments (Belmont Report)• Human Radiation Experiments• Gene Transfer Experiment

West Virginia Clinical and Translational Science Institute

Historical Perspective

Past transgressions lead to the need for laws that protect the rights and welfare of human subjects.• Nuremberg Doctors Trial of 1946 (Nuremberg

Code)• Thalidomide Tragedy (Kefauver-Harris Amendment)• Tuskegee Experiments (Belmont Report)• Human Radiation Experiments• Gene Transfer Experiment

The public trust is sine qua non of clinical research

West Virginia Clinical and Translational Science Institute

• Federal Food, Drug, and Cosmetic Act (FD&C Act)Section 505(i) is the statutory authority for FDA’s oversight of clinical investigations to test safety and effectiveness

• Code of Federal Regulations (CFR)Regulations promulgated under Section 505(i) describing FDA’s authority over the conduct of clinical investigations including

-Sponsor Responsibilities-Clinical Investigator Responsibilities

• Guidance – advisory only, to assist clinical investigators and sponsors in complying with the regulations

• FDA Form 1572 – by signing this form, an investigator agrees to conduct a study in accordance with the protocol and applicable regulations and to provide adequate supervision of a study

Legal Framework

West Virginia Clinical and Translational Science Institute

Good Clinical Practice (GCP): A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.

Legal Framework (cont.)

West Virginia Clinical and Translational Science Institute

The Clinical Investigator

• An individual who actually conducts a study (i.e. under whose immediate direction the drug is dispensed to a subject.)

• In the event an investigation is conducted by a team of individuals, the investigator is the responsible leader of the team.

[21 CFR 312.3]

West Virginia Clinical and Translational Science Institute

Investigator Roles

• Good Clinical Practice (GCP) in FDA regulated research is not the same ‐as good clinical practice in caring for patients

• For example, FDA regulations have very specific requirements for following the protocol, recordkeeping, and drug accountability

• Regulations are designed to:-Ensure the quality and integrity of data collected in clinical trials

-Ensure that the rights, safety and welfare of research participants are protected

West Virginia Clinical and Translational Science Institute

Commitments on Form 1572

• Personally conduct or supervise investigation • Follow protocol • Ensure all persons assisting is study are informed of obligations • Inform subjects that drugs are being used for investigational

purposes • Ensure informed consent (21 CFR Part 50) and IRB review, approval

and reporting (21 CFR Part 56) • Report to sponsor adverse events (21 CFR 312.64) • Maintain adequate and accurate records and make them available for

inspection in accordance with 21 CFR 312.68 • Ensure initial and continuing review by an IRB and report all changes

to research and unanticipated problems involving risks to subjects, not make any changes without IRB approval except where necessary to eliminate immediate hazards

• Comply with other requirements in 21 CFR 312

West Virginia Clinical and Translational Science Institute

Frequently Asked Questions Form 1572

Why does this form need to be completed by an investigator?

West Virginia Clinical and Translational Science Institute

Frequently Asked Questions Form 1572

Why does this form need to be completed by an investigator?

1) To provide the sponsor with information about the investigator’s qualifications and clinical site. 2) To inform the investigator of his/her obligations and obtain the investigator’s commitment to follow pertinent FDA regulations. Making willfully false statement is a criminal offense.

West Virginia Clinical and Translational Science Institute

Frequently Asked Questions Form 1572

Does the 1572 need to be submitted to FDA?

West Virginia Clinical and Translational Science Institute

Frequently Asked Questions Form 1572

Does the 1572 need to be submitted to FDA?

No. Although the sponsor is required to collect 1572 from the investigator, FDA does not require the form to be submitted to the agency.

West Virginia Clinical and Translational Science Institute

Frequently Asked Questions Form 1572

Are CVs required to be signed and dated?

West Virginia Clinical and Translational Science Institute

Frequently Asked Questions Form 1572

Are CVs required to be signed and dated?

No. FDA regulations do not require a CV to be signed and dated. The investigator’s dated signature on the 1572 is sufficient to attest to the accuracy of the CV or other statement of qualifications submitted.

West Virginia Clinical and Translational Science Institute

Investigator Responsibilities General responsibilities (312.60)Control of investigational drug (312.61)Record keeping and retention (312.62)

Maintaining adequate records of the disposition of the drug Accurate case histories that record all observations, and Other data pertinent to the investigation on each individual

administered the investigational drug or employed as a control in the investigation

An investigator is required to maintain investigation records for: 2 years following the data a marketing application is

approved for the drug for the indication for which it is being investigated

2 years after the investigation is discontinued and FDA is notified if no application is to be filed or if the application has not approved for such indication

West Virginia Clinical and Translational Science Institute

Investigator Responsibilities (cont.)Investigator reports (312.64)

Progress reports Safety reports

o Promptly report any adverse event that may reasonably be regarded as caused by, or probably caused by, the drug (err on the side of reporting)

o Immediately report any adverse event that is alarming (e.g. an unexpected event that is serious or life threatening)‐

Final reportFinancial disclosure

West Virginia Clinical and Translational Science Institute

FDA Guidance Investigator Responsibilities

• Outlines FDA expectations for study oversight Appropriate delegation of study tasks

• Appropriate training of study staff • Appropriate supervision of conduct of ongoing

study • Appropriate oversight of third parties involved in

the study (e.g. Site Management Organizations, outside labs specifically retained to conduct study assessments)

West Virginia Clinical and Translational Science Institute

FDA Guidance Investigator Responsibilities (Cont.)

Outlines FDA expectations for protecting the rights, safety, and welfare of subjects • Provision of reasonable medical care for

issues related to study participation (e.g.to manage an adverse event)

• Facilitation of care for other health issues that might arise during the study

• Avoiding exposure of subjects to unreasonable risks

West Virginia Clinical and Translational Science Institute

Ready for some GCP Questions?

West Virginia Clinical and Translational Science Institute

West Virginia Clinical and Translational Science Institute

West Virginia Clinical and Translational Science Institute

West Virginia Clinical and Translational Science Institute

West Virginia Clinical and Translational Science Institute

West Virginia Clinical and Translational Science Institute

West Virginia Clinical and Translational Science Institute

West Virginia Clinical and Translational Science Institute

West Virginia Clinical and Translational Science Institute

West Virginia Clinical and Translational Science Institute

West Virginia Clinical and Translational Science Institute

West Virginia Clinical and Translational Science Institute

West Virginia Clinical and Translational Science Institute

West Virginia Clinical and Translational Science Institute

Questions?

Thank You

Made possible by IDeA CTR support – NIH/NIGMS Award Number U54GM104942

www.wvctsi.org