“So You Think You Know GCP …” Session S794 Jill Matzat, RN, BSN, CCRA, CCRT President, Medical Research Management & CRA Solutions, Inc. Paul Below, CCRA, CCRT Clinical Research Consultant, P. Below Consulting, Inc.

Disclosure Jill Matzat and Paul Below have no relevant financial relationships in relation to this educational activity

Background This presentation was developed to counter numerous misconceptions and myths about Good Clinical Practice overheard by the presenters during their careers This presentation is intended to teach GCP concepts using a quiz format (audience polling is available via text message voting)

Learning Objectives Define Good Clinical Practice (GCP) Differentiate between FDA requirements (stated in regulation) and FDA recommendations (stated in guidance documents) in several key areas Identify several circumstances where “industry best standard” practices exist that go above and beyond what the FDA requires and even recommends

What is Good Clinical Practice? Good Clinical Practice (GCP) is a unified standard for designing, conducting, recording, and reporting trials that involve human subjects GCP is composed of many parts that cannot be found in any one book or place

GCP Other Federal Regulations FDA Regulations (21 CFR) State Law Local Law (Institutional and IRB Policies) FDA Guidance Documents ICH Guidelines for GCP Sponsor SOPs Industry Best Practices

So You Think Know GCP … The following slides are a series of questions to test your knowledge of GCP You will be able to submit your answers via text messaging All answers are anonymous (no one is identified by name or phone number)

How To Vote via Texting Example Question: What is your favorite color? Blue(72612) Red(72613) Green(72614) Yellow(72615) To vote, text the corresponding keyword to NOTE: Standard text messaging rates apply.

Some Notes on Terminology “The FDA requires” = it is specified in regulation “The FDA recommends” = it is specified in an FDA guidance document

Informed Consent Question

FDA regulations require the following: AnswerKeyword The ICF must be signed by the subject The ICF must be signed by the person obtaining consent The ICF must be signed by the investigator Every page of the ICF must be initialed by the subject All of the above Text your answer (keyword) to 22333

FDA regulations require the following: AnswerKeyword The ICF must be signed by the subject The ICF must be signed by the person obtaining consent The ICF must be signed by the investigator Every page of the ICF must be initialed by the subject All of the above Per 21 CFR 50.27, the informed consent form should be “signed and dated by the subject or the subject's legally authorized representative at the time of consent” However, FDA guidance (ICH GCP) also recommends that the form be signed by the person obtaining the consent

Other ICF Misconceptions It is acceptable for the study staff to date the consent for the subject if they forgot to do so A spouse can always function as a “legally authorized representative” Consent forms must be written at a 6th grade reading level

Form FDA 1572 Question

FDA guidance recommends the following: AnswerKeyword The signed 1572 must be submitted to the FDA prior to the Investigator’s participation in the trial The 1572 must be updated when new sub- investigators are added to Box # The Principal Investigator must be a physician Only one Principal Investigator should be listed in Box # All of the above Text your answer (keyword) to 22333

FDA guidance recommends the following: AnswerKeyword The signed 1572 must be submitted to the FDA prior to the Investigator’s participation in the trial The 1572 must be updated when new sub- investigators are added to Box # The Principal Investigator must be a physician Only one Principal Investigator should be listed in Box # All of the above A recent FDA Guidance Document was issued in May 2010 to clarify the agency’s expectations regarding completion the form.

Other 1572 Misconceptions Must be completed on a double-sided form Must be typed Study Coordinators should not be listed as Sub- Investigators in Box #6 All rotating study staff (e.g., residents, fellows) must be listed as Sub-Investigators in Box #6

Curriculum Vitae (CV) Question

FDA regulations require the following: AnswerKeyword CVs must be collected for all investigators (PI and all Sub-investigators) CVs must be collected at the beginning of the study CVs must be “up-to-date” CVs must be signed and dated by the completer All of the above Text your answer (keyword) to 22333

FDA regulations require the following: AnswerKeyword CVs must be collected for all investigators (PI and all Sub-investigators) CVs must be collected at the beginning of the study CVs must be “up-to-date” CVs must be signed and dated by the completer All of the above Per 21 CFR (a)(6)(iii)(a), Sponsors need to include in their initial IND submission a statement of the qualifications (curriculum vitae or other statement of qualifications) of each Principal Investigator and only the names of each Sub-Investigator

FDA regulations require the following: AnswerKeyword CVs must be collected for all investigators (PI and all Sub-investigators) CVs must be collected at the beginning of the study CVs must be “up-to-date” CVs must be signed and dated by the completer All of the above However, FDA guidance (ICH GCP) recommends that the Investigator CV be “up-to-date” (4.1.1) and be collected for all PIs and Sub-Investigators (8.2.10)

Case Report Form Question

FDA guidance recommends the following: AnswerKeyword CRF corrections should be dated and initialed and should not obscure the original entry When CRFs are used as source documents, they should be specified in the protocol Sponsors may make changes to the CRF data with the authorization of the investigator All of the above None of the above Text your answer (keyword) to 22333

FDA guidance recommends the following: AnswerKeyword CRF corrections should be dated and initialed and should not obscure the original entry When CRFs are used as source documents, they should be specified in the protocol Sponsors may make changes to the CRF data with the authorization of the investigator All of the above None of the above All of the above are specified in ICH GCP

FDA guidance recommends the following: AnswerKeyword CRF corrections should be dated and initialed and should not obscure the original entry When CRFs are used as source documents, they should be specified in the protocol Sponsors may make changes to the CRF data with the authorization of the investigator All of the above None of the above There is nothing in FDA regulation or guidance that specifies that CRF corrections must be made with a single line through the original entry

Investigational Product Question

FDA regulations require the following: AnswerKeyword Investigational product (IP) must be stored in a secure location with limited access IP must be environmentally monitored and controlled IP must be labeled with “Caution: New Drug (or Device) -- Limited by Federal (or United States) law to investigational use.” All unused IP must be returned to the sponsor at the end of the trial Text your answer (keyword) to 22333

FDA regulations require the following: AnswerKeyword Investigational product (IP) must be stored in a secure location with limited access IP must be environmentally monitored and controlled IP must be labeled with “Caution: New Drug (or Device) -- Limited by Federal (or United States) law to investigational use.” All unused IP must be returned to the sponsor at the end of the trial Labeling requirements are specified for drugs in 21 CFR and for devices in 21 CFR 812.5

FDA regulations require the following: AnswerKeyword Investigational product (IP) must be stored in a secure location with limited access IP must be environmentally monitored and controlled IP must be labeled with “Caution: New Drug (or Device) -- Limited by Federal (or United States) law to investigational use.” All unused IP must be returned to the sponsor at the end of the trial The only language in the device or drug regulations related to IP storage concerns investigational drugs that are controlled substances (21 CFR , “storage of the investigational drug in a securely locked, substantially constructed cabinet, or other securely locked, substantially constructed enclosure, access to which is limited …”)

FDA regulations require the following: AnswerKeyword Investigational product (IP) must be stored in a secure location with limited access IP must be environmentally monitored and controlled IP must be labeled with “Caution: New Drug (or Device) -- Limited by Federal (or United States) law to investigational use.” All unused IP must be returned to the sponsor at the end of the trial CFR indicates sponsors “may authorize alternative disposition” for unused investigational drugs 21 CFR indicates that investigators can “otherwise dispose of the device as the sponsor directs”

Emergency Use of IP Question

If IP is used in a life-threatening situation prior to obtaining informed consent, what is the required time frame to report this to the IRB? AnswerKeyword Promptly Within 24 hours Within 3 calendar days Within 3 working days Within 5 working days Text your answer (keyword) to 22333

If IP is used in a life-threatening situation prior to obtaining informed consent, what is the required time frame to report this to the IRB? AnswerKeyword Promptly Within 24 hours Within 3 calendar days Within 3 working days Within 5 working days Reporting requirements for all products are specified in 21 CFR 50.23: “shall be submitted to the IRB within 5 working days after the use of the test article”

Regulatory Document Question

FDA regulations require that the following documents be signed by the investigator: AnswerKeyword Trial Delegation Log Completed and final case report forms Financial disclosure forms Protocol signature pages All of the above None of the above Text your answer (keyword) to 22333

FDA regulations require that the following documents be signed by the investigator: AnswerKeyword Trial Delegation Log Completed and final case report forms Financial disclosure forms Protocol signature pages All of the above None of the above The only document specified by FDA regulation that must be signed by the investigator is the Form FDA 1572 (for drugs) or the Investigator Agreement (for devices)

Closing Thoughts Most FDA requirements are vague and open to some interpretation Most of what we do in clinical research is driven by our own industry best practices and not FDA requirements or even recommendations Be careful when telling an investigator site, “You have to do this because the FDA requires it” unless you are certain that it is specified by regulation

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Contact Information Jill Matzat Come visit Jill at the Medical Research Management booth in the exhibit hall Paul Below Paul presents again on Monday at 4:15 pm (S831 - You've Discovered Fraud - Now What Do You Do?) Poll results available at