SoCRA Review: Investigator Roles and Responsibilities in Clinical Research John Naim, PhD Director Clinical Trials Research Unit West Virginia University March 20, 2015

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 Course http://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

Legal Framework 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 West Virginia Clinical and Translational Science Institute

Legal Framework (cont.) 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. 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 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) Immediately report any adverse event that is alarming (e.g. an unexpected event that is serious or life‐threatening) Final report Financial 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 www.wvctsi.org Made possible by IDeA CTR support – NIH/NIGMS Award Number U54GM104942 West Virginia Clinical and Translational Science Institute